Genetic and experimental evidence for the involvement of the CD6 lymphocyte receptor in psoriasis

Abstract

Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors. Available evidence supports CD6, a lymphocyte surface receptor mostly expressed by T cells, as a putative target in autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders, including psoriasis. Here, we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines, namely, interleukin-17A. Thus, isolated CD4CD62L T cells from CD6-deficient mice displayed decreased in vitro T-helper type 17 polarization. Second, a statistically significant association between CD6 single-nucleotide polymorphisms (rs17824933, rs11230563 and rs12360861) and more severe forms of psoriasis was demonstrated in a cohort of 304 patients at three public hospitals from the metropolitan area of Barcelona. Taken together, these results provide new supportive evidence of the contribution of the CD6 lymphocyte receptor in psoriasis at both experimental and clinical levels.Cellular and Molecular Immunology advance online publication, 11 December 2017; doi:10.1038/cmi.2017.119.

Attenuation of Murine Collagen‐Induced Arthritis by Targeting CD6

“…Recent data also suggest that CD6 may be very important in T cell–driven autoimmune diseases both in humans and in animal models. Loci associated with CD6 affect susceptibility to multiple sclerosis (MS) and Behçet's syndrome, and the severity of psoriasis . Notably, an anti‐CD6 mAb is effective in the treatment of psoriasis .…”

Multifaceted effects of soluble human CD6 in experimental cancer models

“…Open access cd6 -/mice of DBA/1 background. 36 The fact that B cells (in contrast to T cells) constitutively express ALCAM 39 and that ALCAM-mediated cell-to-cell homotypic interaction is necessary to sustain proper proliferative responses in different cell types [40][41][42] may be behind our observations.…”

The role of CD6 in autoimmune diseases

“…CD6associated single nucleotide polymorphisms controlled the extent and severity of skin involvement and the incidence of psoriatic arthritis in a cohort of psoriasis patients. 1 It will now be important to undertake functional genomic studies to elucidate the mechanisms underlying these observations, which could include regulation of CD6 expression and perhaps differential utilization of alternative splicing to generate an altered balance of CD6 isoforms.…”

“…In a recent publication in the Cellular and Molecular Immunology, Consuega-Fernandez and colleagues present new data from patients with psoriasis, linking the CD6 lymphocyte surface structure to the pathogenesis of this disease. 1 In this commentary, I will discuss these new findings in the context of accumulating evidence for important roles of CD6 in a variety of autoimmune disorders. Although CD6 was one of the earliest "CD antigens" to be described, it is only recently that attention has refocused on the potential for CD6 as a treatment target in immune-mediated diseases.…”