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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 CD4+CD62L+ 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.

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Acknowledgements

We thank Francesc Calafell and Elena Bosch (Institute of Evolutionary Biology, University Pompeu Fabra, Barcelona) for statistical analysis support and critically reviews of the manuscript. The work is supported by grants from the Spanish Ministerio de Economía y Competitividad (Plan Nacional I+D+i, SAF2013-46151-R and SAF2016-80535-R to FL), co-financed by the European Development Regional Fund ‘A way to achieve Europe’ ERDF. FA is supported by the Sara Borrell fellowship CD15/00016 from Instituto de Salud Carlos III.

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Correspondence to Francisco Lozano.

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Keywords

  • ALCAM
  • CD5
  • CD6
  • lymphocyte
  • psoriasis

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