Selective response of circulating CLA+ T cells to antigens involved in cutaneous disease triggering.
Abstract
Focusing on the study of human memory CLA+ T cells to understand psoriasis pathology constitutes an innovative approach to explore the pathological mechanism of this chronic cutaneous inflammatory disease. CLA+ T cells can be considered peripheral cell biomarkers in the study of T-cell mediated human skin diseases. During the last few years, new evidences have been found that link streptococcal infection with IL-17 response in psoriasis by studying the interaction between Streptococcus pyogenes with CLA+ T cells and autologous epidermal cells. S. pyogenes constitutes the best clinically characterized trigger of psoriasis and by exploring its effect on CLA+ T cells and epidermal cells in psoriasis may allow understanding psoriasis by using patient’s clinical samples ex vivo.
Keywords
- psoriasis
- CLA+ T cells
- translational research
- Streptococcus pyogenes
- IL17
1. CLA+ T cells and the regional cutaneous immune system
The adaptive immune responses taking place during cutaneous chronic inflammation in psoriasis preferentially involve a subset of memory T lymphocytes, which are related to the skin and that belong to the cutaneous immune system, and constitute one of the best characterized regional immune systems of the body and known for decades [1]. In the humans, the cutaneous lymphocyte-associated antigen (CLA) is a surface cell marker that allows identifying T cells that belong to the cutaneous immune system. The CLA antigen is a carbohydrate expressed by 15% of human circulating T cells, and on most (>90%) skin-infiltrating T cells, contrary to other inflamed organs [2]. CLA is expressed preferentially on memory antigen-experienced T cells.
The CLA is one of the adhesion molecule that, together with chemokine receptors, allows T cells to selectively migrate to the skin, in either homeostatic or inflammatory conditions, by binding to endothelial cell wall via adhesion molecules or ligands. The molecular interactions between CLA/E-selectin, very late antigen-4 (VLA-4)/vascular cell adhesion protein-1 (VCAM-1), lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1), and chemokine ligands for chemokine, C-C motif receptor (CCR) 10, CCR4, CCR6, and CCR8 constitute a code bar system enabling skin infiltration [3].
The importance of circulating CLA+ T cells for understanding the skin immune system is not only based on their capacity to selectively migrate to skin, but also on the fact that these circulating memory T cells are functionally related to the immune response taking place in the cutaneous inflamed lesions. This feature is based on the recirculating capacity of those cells between lesional skin and blood during cutaneous inflammation in psoriasis [3]. The adhesive interaction between LFA-1 and ICAM-1 is one of the mechanisms involved in the transendothelial migration of CLA+ T cells [4]. Interestingly, the blockade of LFA-1/ICAM-1 interaction in psoriasis patients with anti-LFA-1 in patients blocks extravasation and leads to CLA+ T cell lymphocytosis. Such accumulation of CLA+ T cells in the blood has clinical relevance since skin relapse may develop after stopping the anti-LFA-1 treatment [3].
The function and phenotype of circulating CLA+ T cells in T-cell mediated skin disease have been studied in many different human skin conditions. Those skin-seeking memory T cells respond to antigens, allergens, or superantigens that play a key role in disease triggering of different human T-cell mediated skin diseases, see Table 1. In addition, their phenotype and function are related to clinical status of the patient. For these reasons, those cells are considered peripheral cell biomarkers of T-cell mediated human cutaneous diseases [3, 5, 6].
2. Translational research and clinically relevant pathological mechanism of psoriasis
The innovation in psoriasis treatment has benefited from the continuous bidirectional flow of information from the bedside of clinic to the laboratory and vice versa [7]. Innovative pathogenic concepts have been tested in patients through the use of targeted therapeutics leading to clinically validated mechanism of disease. Those mechanisms that started as a merely scientific hypothesis of disease that can be proven to be relevant in the clinic by specific biological treatments allow improvement in the therapeutic arsenal for patients. At present, it is possible to understand psoriasis from several of its clinically relevant mechanism/targets that has been validated in the clinic since that has provided clinical benefit in patient. The current clinically validated concept of psoriasis is summarized in Tables 2 and 3. During the last two decades approximately, it has been demonstrated the key role of the IL-23/Th17 axis in psoriasis [8]. The journey to the current situation in psoriasis treatment started by evidencing that T-cell activity in psoriasis had real implications for the patients. Thus, depletion of T cells [9, 10], costimulation [11], and inhibition of their migration from blood to skin demonstrated improvement in the clinical severity [12]. Not only memory T cells are of translational relevance in psoriasis, but also TNF-α is a key cytokine for this disease. Although originally thought not to be associated to T-cell function, lately it was demonstrated that TNF-α neutralization affects Th17 function [13]. The introduction of ustekinumab, a monoclonal antibody that neutralizes both IL-12 and IL-23, cytokines involved in differentiation of Th1 and Th17 cells, respectively, marked the initiation of the IL-23/Th17 axis era [14]. In contrast to the increased amounts of IL-23, there is no marked increase of IL-12 in psoriatic lesion in comparison to nonlesional or healthy [15]. It became evident that the ustekinumab clinical efficacy was related to inhibition of the IL-23 biological effect.
Biological treatment | Mechanism action | Target | Relevance |
---|---|---|---|
DAB389-IL-2 | Toxin acting on cells expressing IL-2 receptor | CD25 | T-cells are important in psoriasis [9] |
CTLA4-Ig | T cell costimulation blockade | CD80, CD86 | Blocking T cell activation improve psoriasis [11] |
LFA-3-Ig | Memory T cell depletion | CD2 | Memory T cells are relevant in psoriasis [10] |
Anti-LFA-1 | T cell migration and T-cell costimulation inhibitor | LFA-1 | Migration of T cells to psoriasis lesion is involved in disease [12] |
Anti-TNF-α | Neutralization of biological activity | TNF-α | Biological activity of TNF-α is involved in psoriasis [65] |
Anti-p40 (IL-12/ IL-23) | Neutralization of biological activity | p40 (IL-12/IL-23) | Cytokines involved in generating Th1 and Th17 are relevant in psoriasis [14] |
Anti-IL-17A | Neutralization of I biological activity | IL-17A | Other cytokines besides TNF play a role in psoriasis [66] |
Anti-IL-17RA | Blockade of receptor | IL-17RA | IL-17 signaling plays a relevant role in psoriasis [67] |
Anti-IL-23p19 | Neutralization of biological activity | IL-23p19 | IL-23/Th17 axis play essential role in psoriasis [16] |
Biological treatment | Mechanism of action | Target | Relevance |
---|---|---|---|
IL-8 | Neutralization of biological activity | IL-8 | IL-8 is not clinically validated in psoriasis [68] |
IFN-γ | Neutralization of biological activity | IFN-γ | IFN-γ is not clinically validated in psoriasis [69] |
IFN-α | Neutralization of biological activity | IFN-α | IFN-α is not clinically validated in psoriasis [70] |
IL-22 | Neutralization of biological activity | IL-22 | IL-22 is not clinically validated in psoriasis [71] |
The next step was to translate the consequence of blocking the IL-23, a cytokine involved in the differentiation of T cells producing IL-17, into the clinic. The selective inhibition of the biological activity of IL-17A, or its receptor IL-17RA, has demonstrated an impressive clinical efficacy in patients in the clinical trials. The most innovative approach currently is to block selectively IL-23, which also has confirmed the clinical relevance of specifically blocking the IL-23/Th17 in psoriasis [16].
In contrast to the mediators or cells that have confirmed its relevance in psoriasis due to its clinical importance in reducing disease severity, there are several well-known mechanisms present in psoriasis that have not been validated in the clinic, since their biological neutralization in the patient has not brought clinical benefit, see Table 3. Mediators such us IFN-γ, IFN-α, IL-8, and IL-22 have been neutralized in patients without significant clinical improvement.
When studying psoriasis triggering factors from the translational point of view, perhaps the best characterized environmental factor is throat infection by β-hemolytic streptococci. As it is commented below, there is a great body of evidences that associate streptococcal infection with psoriasis flares or exacerbations in both guttate and plaque psoriasis. This can be considered a translational opportunity of studying psoriasis immune response from a different and innovative perspective.
3. Streptococcal pyogenes infection and psoriasis
Throat infection by β-hemolytic streptococci has been associated with both the flare and exacerbation of psoriasis [17–19]. In guttate psoriasis, this infection precedes clinical cutaneous symptoms in 56–97% of the cases [20]. Interestingly, chronic plaque psoriasis patients are more susceptible to throat infections by
An immunological model has been proposed to explain how an infection taking place in the throat can lead to a chronic inflammation in a distant tissue such as the skin. One interesting observation is to note that dendritic cells from tonsils and upper respiratory truck are capable of generating some skin-tropic CLA+ T cells [27], thus indicating that those cells can acquire antigen-specificity for microbes infecting noncutaneous sites. In this regard, streptococcal superantigens promote the expression of CLA on T cells [28], as well as the activation and expansion of CLA+ T cells, at least from guttate psoriasis. Guttate psoriasis is an acute form of psoriasis, which erupts as small drop-shaped papules, and is frequently associated with streptococcal throat infection. In particular, accumulation of Vβ2+ T cells in acute guttate lesions has been reported, a variable β chain expressed on T cells that are preferentially expanded through the streptococcal pyrogenic exotoxin (SPE)-C [29], which contained T cells with different junctional sequences in the CDR3 region, thus supporting a superantigen-driven expansion. However, as psoriasis progresses, such superantigen hypothesis does not seem to explain the presence of identical TCR rearrangements in plaque psoriasis patients, probably indicating that a stable antigen-specific T-cell response is involved for longer stages of the disease [30, 31]. Interestingly, T-cell lines isolated from psoriatic lesions have shown strong cross-reactivity to streptococcal antigens [32]. Furthermore, restricted TCRVβ spectratypes shared by CLA+ T cells in streptococcal angina, but not by CLA− T cells, with T cells in psoriasis skin lesions supports the idea of the existence of a tonsillar source of antigen-driven T-cell expansion that then migrate to the skin [33]. Altogether, streptococcal superantigens could facilitate at least early migration of tonsillar T cells to the skin by upregulating CLA expression and could be especially involved in guttate-type flares.
Despite the evidence of streptococcal involvement in psoriasis course, the use of antibiotics has not proven effectiveness in psoriasis [36]. However, it might be explained by the fact that streptococci can exist in intracellular reservoirs in the tonsillar epithelia and macrophages, and that could not be affected by the use of antibiotics. Then, this quiescent load could be reactivated and cause disease symptoms again, whereas tonsillectomy, which has been associated to clinical improvement, might remove this hidden pool of streptococci [22, 37].
Other entry routes for
4. Streptococcus pyogenes : an innate trigger that induces IL-17 production through skin-related memory CLA+ T cells in psoriasis
Analyzing the antigen-specific immune responses with clinically relevant stimuli in responding patients allows identifying pathologic translational mechanisms of several immunologic diseases, including psoriasis. This experimental approach can be reproduced
Since the closest and clearest relationship between streptococcal infection and subsequent onset of lesions has been described for guttate-type psoriasis, the evaluation of immune responses in the context of
A second study based on this
The importance of Th17 role in initial steps of psoriasis development is also supported by other findings, such as the high levels in serum of IL-17 found in patients with early spreading guttate form [47]. Even a bimodal immunopathology theory proposes that psoriasis is initiated by IL-1/Th17-dominated responses [48]. In addition to the well-known association of preceding pharyngitis episode, guttate psoriasis onset is mostly confined to individuals carrying the HLA-Cw6 allele [49], a genetic risk factor for early psoriasis. Interestingly, when immune responses from guttate psoriasis samples were classified according with the simultaneous presence of both genetic and environmental factors, that is HLA-Cw6 allele and a prior pharyngitis episode, respectively, the Th17-associated response was higher than that exerted by samples from the other “nonpredisposed” guttate psoriatic individuals. In fact, significant higher levels of IL-17A, IL-17F, and even IL-6, which participates in Th17-differentiation, were found in those “predisposed” guttate psoriasis patients. Furthermore, the treatment of
Therapies targeting the IL-23/Th17-axis are showing the best efficacy rates in terms of percentage of patients reaching PASI improvement. The observation of rapid normalization of hundreds of psoriasis-related genes as soon as 2 weeks after the use of IL-17A or IL-17RA-blocking antibodies [53, 54] may partly explain the importance of IL-17A effects in psoriasis pathology, and why its blockade provides such impressive clinical improvement. Therefore, the characterization of IL-17-targeted transcripts that are rapidly normalized after these therapies could reveal relevant information regarding to the development of skin lesions.
In this regard, Ruiz-Romeu et al. [55] have taken advantage of the use of CLA+ T cell and epidermal cells activated by SE conditioned supernatants to activate normal keratinocytes and to evaluate gene expression of noncharacterized IL-17A targets. In their study, they characterize the expression of
5. Conclusions
The translational approach of developing an
Acknowledgments
The study was funded by FIS/ISCIII 2013 (Ministerio de Economía y Competitividad e Instituto de Salud Carlos III; PI09/2222, PI13/01845 and PI13/01716) and FIS/ISCIII 2016 (PI16/01573 and PI016/99532). This work was supported by European Regional Development Fund grants. E. R. R was granted by a PhD fellowship by the Ministerio de Educación, Cultura y Deporte of the Spanish Government (FPU13/02308).
References
- 1.
Picker L, and Butcher E. Physiological and molecular mechanisms of lymphocyte homing. Annu Rev Immunol. 1992; 10: 561-591. 10.1146/annurev.iy.10.040192.003021 - 2.
Picker L, Michie S, Rott L, Butcher E. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol. 1990; 136: 1053-1068. - 3.
Ferran M, Romeu E, Rincon C, Sagrista M, Gimenez Arnau A, Celada A, Pujol R, Hollo P, Jokai H, Santamaria-Babi L. Circulating CLA+ T lymphocytes as peripheral cell biomarkers in T-cell-mediated skin diseases. Exp Dermatol. 2013; 22: 439-442. 10.1111/exd.12154 - 4.
Santamaria Babi L, Moser R, Perez Soler M, Picker L, Blaser K, Hauser C. Migration of skin-homing T cells across cytokine-activated human endothelial cell layers involves interaction of the cutaneous lymphocyte-associated antigen (CLA), the very late antigen-4 (VLA-4), and the lymphocyte function-associated antigen-1 (LFA-1). J Immunol. 1995; 154: 1543-1550. - 5.
Czarnowicki T, Santamaria-Babi L, Guttman-Yassky E. Circulating CLA+ T cells in atopic dermatitis and their possible role as peripheral biomarkers. Allergy. 2016; 72: 366-372 - 6.
Santamaria Babi L, Perez Soler M, Hauser C, Blaser K. Skin-homing T cells in human cutaneous allergic inflammation. Immunol Res. 1995; 14: 317-324. 90232 [pii];10.1159/000090232 - 7.
Guttman-Yassky, Krueger J. Psoriasis: evolution of pathogenic concepts and new therapies through phases of translational research. Br J Dermatol. 2007; 157: 1103-1115. BJD8135 [pii];10.1111/j.1365-2133.2007.08135.x - 8.
Kim J, Krueger JG. Highly effective new treatments for psoriasis target the IL-23/Type 17 T Cell autoimmune axis. Annu Rev Med. 2017; 68: 255-269. 10.1056/NEJM200107263450403 - 9.
Gottlieb SL, Gilleaudeau P, Johnson R, Estes L, Woodworth TG, Gottlieb AB, Krueger JG: 1995. Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat Med. 1995; 1: 442-447. - 10.
Ellis CN, Krueger GC. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N Engl J Med. 2001; 345: 248-255. 10.1056/NEJM200107263450403 - 11.
Abrams JR, Kelley SL, Hayes E, Kikuchi T, Brown MJ, Kang S, Lebwohl MG, Guzzo CA, Jegasothy BV, Linsley PS, Krueger JG. Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J Exp Med. 2000; 192: 681-694. - 12.
Gottlieb AB, Miller B, Lowe N, Shapiro W, Hudson C, Bright R, Ling M, Magee A, McCall CO, Rist T, Dummer W, Walicke P, Bauer RJ, White M, Garovoy M. Subcutaneously administered efalizumab (anti-CD11a) improves signs and symptoms of moderate to severe plaque psoriasis. J Cutan Med Surg. 2003; 7: 198-207. 10.1007/s10227-002-0118-1 - 13.
Zaba LC, Cardinale I, Gilleaudeau P, Sullivan-Whalen M, Suarez-Farinas M, Fuentes-Duculan J, Novitskaya I, Khatcherian A, Bluth MJ, Lowes MA, Krueger JG. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med. 2007; 204: 3183-3194. jem.20071094 [pii];10.1084/jem.20071094 - 14.
Leonardi CL, Kimball AB, Papp KA, Yeilding N, Guzzo C, Wang Y, Li S, Dooley LT, and Gordon KB. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008; 371: 1665-1674. S0140-6736(08)60725-4 [pii];10.1016/S0140 6736(08)60725-4. - 15.
Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F, Dhodapkar M, Krueger JG. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med. 2004; 199: 125-130. 10.1084/jem.20030451 [doi];199/1/125 - 16.
Sofen H, Smith S, Matheson RT, Leonardi CL, Calderon C, Brodmerkel C, Li K, Campbell K, Marciniak SJ, Wasfi Y, Wang Y, Szapary P, Krueger JG. Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol. 2014; 133: 1032-1040. S0091-6749(14)00181-X [pii];10.1016/j.jaci.2014.01.025 - 17.
Telfer NR, Chalmers RJ, Whale J, Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Arch Dermatol. 1992; 128: 39-42. - 18.
Wardrop P, Weller R, Marais J, Kavanagh G. Tonsillitis and chronic psoriasis. Clin Otolaryngol Allied Sci.1998; 23: 67-68. - 19.
Gudjonsson JE, Thorarinsson AM, Sigurgeirsson S, Kristinsson KG, Valdimarsson H. Streptococcal throat infections and exacerbation of chronic plaque psoriasis: a prospective study. Br J Dermatol. 2003; 149: 530-534. 5552 [pii] - 20.
Prin JC. Psoriasis vulgaris—a sterile antibacterial skin reaction mediated by cross-reactive T cells? An immunological view of the pathophysiology of psoriasis. Clin Exp Dermatol. 2001; 26: 326-332. ced831 [pii] - 21.
El-Rachkidy RG, Hales JM, Freestone PP, Young HS, Griffiths CE, Camp RD Increased blood levels of IgG reactive with secreted Streptococcus pyogenes proteins in chronic plaque psoriasis. J Invest Dermatol. 2007; 127: 1337-1342. S0022-202X(15)33401-1 [pii];10.1038/sj.jid.5700744 - 22.
Thorleifsdottir RH, Eysteinsdottir JH, J. Olafsson JH, Sigurdsson MI, Johnston A, Valdimarsson H, Sigurgeirsson. Throat infections are associated with exacerbation in a substantial proportion of patients with chronic plaque psoriasis. Acta Derm Venereol. 2016; 96: 788-791. 10.2340/00015555-2408 - 23.
Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, Olafsson JH, Sigurdsson MI, Petersen H, Arnadottir S, Gudjonsson JE, Johnston A, Valdimarsson H. Improvement of psoriasis after tonsillectomy is associated with a decrease in the frequency of circulating T cells that recognize streptococcal determinants and homologous skin determinants. J Immunol. 2012; 188: 5160-5165. jimmunol.1102834 [pii];10.4049/jimmunol.1102834 - 24.
Hone SW, Donnelly MJ, Powell F, Blayney AW. Clearance of recalcitrant psoriasis after tonsillectomy. Clin Otolaryngol Allied Sci. 1996; 21: 546-547. - 25.
Nyfors A, Rasmussen PA, Lemholt K, Eriksen B. Improvement of recalcitrant psoriasis vulgaris after tonsillectomy. J Laryngol Otol. 1976; 90: 789-794. - 26.
Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, Olafsson JH, Sigurdsson MI, Petersen H, Gudjonsson JE, Johnston A, Valdimarsson H. Patient-reported outcomes and clinical response in patients with moderate-to-severe plaque psoriasis treated with tonsillectomy: a randomized controlled trial. Acta Derm Venereol. 2017; 97: 340-345. - 27.
Sabat R, Philipp S, Hoflich C, Kreutzer S, Wallace E, Asadullah K, Volk HD, Sterry W, Wolk K. Immunopathogenesis of psoriasis. Exp Dermatol. 2007; 16: 779-798. EXD629 [pii];10.1111/j.1600-0625.2007.00629.x - 28.
Leung DY, Gately M, Trumble A, Ferguson-Darnell B, Schlievert PM, Picker LJ. Bacterial superantigens induce T cell expression of the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen, via stimulation of interleukin 12 production. J Exp Med. 1995; 181: 747-753. - 29.
Leung DY, Travers JB, Giorno R, Norris DA, Skinner R, Aelion J, Kazemi LV, Kim MH, Trumble AE, Kotb M. Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis. J Clin Invest. 1995; 96: 2106-2112. 10.1172/JCI118263 - 30.
Prinz JC, Vollmer S, Boehncke WH, Menssen A, Laisney I, Trommler P. Selection of conserved TCR VDJ rearrangements in chronic psoriatic plaques indicates a common antigen in psoriasis vulgaris. Eur J Immunol. 1999; 29: 3360-3368. 10.1002/(SICI)1521-4141(199910)29:10<3360::AID-IMMU3360>3.0.CO;2-G [pii];10.1002/(SICI)1521-4141(199910)29:10<3360::AID-IMMU3360>3.0.CO;2-G - 31.
Vollmer S, Menssen A, Prinz JC. Dominant lesional T cell receptor rearrangements persist in relapsing psoriasis but are absent from nonlesional skin: evidence for a stable antigen-specific pathogenic T cell response in psoriasis vulgaris. J Invest Dermatol. 2001; 117: 1296-1301. S0022-202X(15)41455-1 [pii];10.1046/j.0022-202x.2001.01494.x - 32.
Valdimarsson H, Thorleifsdottir RH, Sigurdardottir SL, Gudjonsson JE, Johnston A. Psoriasis—as an autoimmune disease caused by molecular mimicry. Trends Immunol. 2009; 30: 494-501. S1471-4906(09)00153-7 [pii];10.1016/j.it.2009.07.008 - 33.
Diluvio L, Vollmer S, Besgen P, Ellwart JW, Chimenti S, Prinz JC. Identical TCR beta-chain rearrangements in streptococcal angina and skin lesions of patients with psoriasis vulgaris. J Immunol. 2006; 176: 7104-7111. 176/11/7104 - 34.
Gudjonsson JE, Johnston A, Sigmundsdottir H, Valdimarsson H. Immunopathogenic mechanisms in psoriasis. Clin Exp Immunol. 2004; 135: 1-8. 2310 [pii] - 35.
Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, Olafsson JH, Sigurdsson ML, Petersen H, Arnadottir S, Gudjonsson JE, Johnston A, Valdimarsson H. Improvement of psoriasis after tonsillectomy is associated with a decrease in the frequency of circulating T cells that recognize streptococcal determinants and homologous skin determinants. J Immunol. 2012; 188: 5160-5165. jimmunol.1102834 [pii];10.4049/jimmunol.1102834 - 36.
Owen CM, Chalmers RJ, O'Sullivan T, Griffiths CE. A systematic review of antistreptococcal interventions for guttate and chronic plaque psoriasis. Br J Dermatol. 2001 145: 886-890. - 37.
Osterlund A, Popa R, Nikkila T, Scheynius A, Engstrand L. Intracellular reservoir of Streptococcus pyogenes in vivo: a possible explanation for recurrent pharyngotonsillitis. Laryngoscope. 1997; 107: 640-647. - 38.
Fahlen A, Engstrand L, Baker BS, Powles A, Fry L. Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. Arch Dermatol Res. 2012; 304: 15-22. 10.1007/s00403-011-1189-x - 39.
Mallbris L, Larsson P, Bergqvist S, Vingard E, Granath F, Stahle M. Psoriasis phenotype at disease onset: clinical characterization of 400 adult cases. J Invest Dermatol. 2005; 124: 499-504. S0022-202X(15)32215-6 [pii];10.1111/j.0022-202X.2004.23611.x - 40.
Ferran M, Galvan AB, Rincon C, Romeu ER, Sacrista M, Barboza E, Gimenez-Arnau A, Celada A, Pujol RM, Santamaria-Babi LF. Streptococcus induces circulating CLA(+) memory T-cell-dependent epidermal cell activation in psoriasis. J. Invest Dermatol. 2013; 133: 999-1007. S0022-202X(15)36179-0 [pii];10.1038/jid.2012.418 - 41.
Nograles KE, Zaba LC, Guttman-Yassky E, Fuentes-Duculan J, Suarez-Farinas M, Cardinale I, Khatcherian A, Gonzalez J, Pierson JC, White TR, Pensabene C, Coats I, Novitskaya I, Lowes MA, Krueger JG. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol. 2008; 159: 1092-1102. BJD8769 [pii];10.1111/j.1365-2133.2008.08769.x - 42.
Vissers, WH, Arndtz CH, Muys L, Van Erp PE,. de Jong E M, and van de Kerkhof PC. 2004. Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the margin zone of spreading psoriatic lesions in contrast to cells expressing natural killer receptors, which appear late. Br J Dermatol. 150: 852-859. 10.1111/j.1365-2133.2004.05863.x [doi];BJD5863 - 43.
Davison SC, Ballsdon A, Allen MH, Barker JN. Early migration of cutaneous lymphocyte-associated antigen (CLA) positive T cells into evolving psoriatic plaques. Exp Dermatol. 2001; 10: 280-285. exd100408 - 44.
Langley RG, Krueger GK, Griffiths CE. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis. 2005; 64(Suppl 2): ii18–ii23. 64/suppl_2/ii18 [pii];10.1136/ard.2004.033217 - 45.
Weisenseel P, Laumbacher B, Besgen P, Ludolph-Hauser D, Herzinger T, Roecken M, Wank R, Prinz JC. Streptococcal infection distinguishes different types of psoriasis. J. Med. Genet. 2002; 39: 767-768. - 46.
Ruiz-Romeu E, Ferran M, Sagrista M, Gomez J, Gimenez-Arnau A, Herszenyi K, Hollo P, Celada A, Pujol R, Santamaria-Babi LF. Streptococcus pyogenes -induced cutaneous lymphocyte antigen-positive T cell-dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis. J Allergy Clin Immunol. 2016; 138: 491-499. S0091-6749(16)00360-2 [pii];10.1016/j.jaci.2016.02.008 - 47.
Choe YB, Hwang YJ, Hahn HJ, Jung JW, Jung HJ, Lee YW, Ahn KJ, Youn JI. A comparison of serum inflammatory cytokines according to phenotype in patients with psoriasis. Br J Dermatol. 2012; 167: 762-767. 10.1111/j.1365-2133.2012.11038.x - 48.
Christophers E, Metzler G, Rocken M. Bimodal immune activation in psoriasis. Br J Dermatol. 2014;170: 59-65. 10.1111/bjd.12631 - 49.
Asumalahti K, Ameen M, Suomela S, Hagforsen E, Michaelsson G, Evans J, Munro M, Veal C, Allen M, Leman J, David BA, Kirby B, Connolly M, Griffiths CE, Trembath RC, Kere J, Saarialho-Kere U, Barker JN. Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. J Invest Dermatol. 2003; 120: 627-632. S0022-202X(15)30213-X [pii];10.1046/j.1523-1747.2003.12094.x - 50.
Chiricozzi A,Guttman-Yassky E, Suarez-Farinas M, Nograles K E, Tian S, Cardinale I, Chimenti S, Krueger JG. Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol. 2011; 131: 677-687. S0022-202X(15)35175-7 [pii];10.1038/jid.2010.340 - 51.
Kim BE, Howell MD, Guttman-Yassky E, Gilleaudeau PM, Cardinale IR, Boguniewicz M, Krueger JG, Leung DY. TNF-alpha downregulates filaggrin and loricrin through c-Jun N-terminal kinase: role for TNF-alpha antagonists to improve skin barrier. J Invest Dermatol. 2011; 131: 1272-1279. S0022-202X(15)35315-X [pii];10.1038/jid.2011.24 - 52.
Roberson ED, Bowcock AM. Psoriasis genetics: breaking the barrier. Trends Genet. 2010; 26: 415-423. S0168-9525(10)00129-0 [pii];10.1016/j.tig.2010.06.006 - 53.
Krueger JG, Fretzin S, Suarez-Farinas M, Haslett PA, Phipps KM, Cameron GS, McColm J, Katcherian A, Cueto I, White T, Banerjee S, Hoffman RW. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012; 130: 145-154. S0091-6749(12)00695-1 [pii];10.1016/j.jaci.2012.04.024 - 54.
Russell CB, Rand H, Bigler J, Kerkof K, Timour M, Bautista E, Krueger JG, Salinger DH, Welcher AA, Martin DA. Gene expression profiles normalized in psoriatic skin by treatment with brodalumab, a human anti-IL-17 receptor monoclonal antibody. J Immunol. 2014; 192: 3828-3836. jimmunol.1301737 [pii];10.4049/jimmunol.1301737 - 55.
Ruiz-Romeu E, Ferran M, Gimenez-Arnau A, Bugara B, Lipert B, Jura J, Florencia EF, Prens EP, Celada A, Pujol RM, Santamaria-Babi LF. MCPIP1 RNase Is Aberrantly Distributed in Psoriatic Epidermis and Rapidly Induced by IL-17A. J Invest Dermatol. 2016; 136: 1599-1607. S0022-202X(16)31153-8 [pii];10.1016/j.jid.2016.04.030 - 56.
Chao J, Dai X, Pena T, Doyle DA, Guenther TM, Carlson MA. MCPIP1 Regulates Fibroblast Migration in 3-D Collagen Matrices Downstream of MAP Kinases and NF-kappaB. J Invest Dermatol. 2015; 135: 2944-2954. S0022-202X(15)60179-8 [pii];10.1038/jid.2015.334 - 57.
Chiricozzi A, Nograles KE, Johnson-Huang LM, Fuentes-Duculan J, Cardinale I, Bonifacio KM, Gulati N, Mitsui H, Guttman-Yassky E, Suarez-Farinas M, Krueger JG. IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model. PLoS One. 2014; 9: e90284. 10.1371/journal.pone.0090284 [doi];PONE-D-13-37082 - 58.
Peric M, Koglin S, Kim SM, Morizane S, Besch R, Prinz JC, Ruzicka T, Gallo RL, Schauber J. IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes. J. Immunol. 2008; 181: 8504-8512. 181/12/8504 - 59.
Santamaria Babi LF, Picker LJ, Perez Soler MT, Drzimalla K, Flohr P, Blaser K, Hauser C. Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen. J Exp Med. 1995; 181: 1935-1940. - 60.
Abernathy-Carver KJ, Sampson HA, Picker LJ, Leung DY. Milk-induced eczema is associated with the expansion of T cells expressing cutaneous lymphocyte antigen. J Clin Invest. 1995. 95: 913-918. 10.1172/JCI117743 - 61.
Torres MJ, Gonzalez FJ, Corzo JL, Giron MD, Carvajal MJ, Garcia V, Pinedo A, Martinez-Valverde A, Blanca M, Santamaria LF. Circulating CLA+ lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal-related T-cell receptor variable segments. Clin Exp Allergy. 1998; 28: 1264-1272. - 62.
Blanca M, Leyva L, Torres MJ, Mayorga C, Cornejo-Garcia J, Antunez-Rodriguez C, Santamaria LF, Juarez C. Memory to the hapten in non-immediate cutaneous allergic reactions to betalactams resides in a lymphocyte subpopulation expressing both CD45RO and CLA markers. Blood Cells Mol Dis. 2003; 31: 75-79. S1079979603000615 - 63.
Koelle DM, Liu Z, McClurkan CM, Topp MS, Riddell SR, Pamer EG, Johnson AS, Wald A, Corey L. Expression of cutaneous lymphocyte-associated antigen by CD8(+) T cells specific for a skin-tropic virus. J Clin Invest. 2002 110: 537-548. 10.1172/JCI15537 - 64.
Ogg GS, Rod DP, Romero P, Chen JL, Cerundolo V. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitilig. J Exp Med. 1998; 188: 1203-1208. - 65.
Oh CJ, Das KM, Gottlieb AB. Treatment with anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions. J Am Acad Dermatol. 2000; 42: 829-830. S0190962200907321 - 66.
Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, Braun D, Banerjee S. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012; 366: 1190-1199. 10.1056/NEJMoa1109997 - 67.
Papp KA, Leonardi C, Menter A, Ortonne JP, Krueger JG, Kricorian G, Aras G, Li J, Russell CB, Thompson EH, Baumgartner S. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med. 2012; 366: 1181-1189. 10.1056/NEJMoa1109017 - 68.
http://www.siliconinvestor.com/readmsgs.aspx?subjectid=24141&msgnum=97&batchsize=10&batchtype=Next - 69.
https://business.highbeam.com/436989/article-1G1-110130198/fontolizumab-protein-design-discontinued-usa - 70.
Bissonnette R, Papp K, Maari C, Yao Y, Robbie G, White WI, Le C, White B. A randomized, double-blind, placebo-controlled, phase I study of MEDI-545, an anti-interferon-alfa monoclonal antibody, in subjects with chronic psoriasis. J Am Acad Dermatol. 2010; 62: 427-436. S0190-9622(09)00686-0 [pii];10.1016/j.jaad.2009.05.042 - 71.
Antoniu SA. Discontinued drugs 2011: pulmonary, allergy, gastrointestinal and arthritis. Expert Opin Investig Drugs. 2012; 21: 1607-1618. 10.1517/13543784.2012.712112