Syndecan-1 regulates psoriasiform dermatitis by controlling homeostasis of IL-17-producing γδ T Cells

Anil Kumar Jaiswal, Mohanraj Sadasivam, Nathan K. Archer, Robert J. Miller, Carly A. Dillen, Advaitaa Ravipati, Pyong Woo Park, Shukti Chakravarti, Lloyd S. Miller, Abdel Rahim A. Hamad

Research output: Contribution to journalArticlepeer-review

Abstract

IL-17 is a potent proinflammatory cytokine that drives pathogenesis of multiple autoimmune diseases, including psoriasis. A major source of pathogenic IL-17 is a subset of γδ T cells (Tγδ17) that acquires the ability to produce IL-17 while developing in the thymus. The mechanisms that regulate homeostasis of Tγδ17 cells and their roles in psoriasis, however, are not fully understood. In this paper, we show that the heparan sulfate proteoglycan syndecan-1 (sdc1) plays a critical role in regulating homeostasis of Tγδ17 cells and modulating psoriasis-like skin inflammation in mice. sdc1 was predominantly expressed by Tγδ17 cells (but not IL-172 Tγδ cells) in the thymus, lymph nodes, and dermis. sdc1 deficiency significantly and selectively increased the frequency and absolute numbers of Tγδ17 cells by mechanisms that included increased proliferation and decreased apoptosis. Adoptive transfer experiments ruled out a significant role of sdc1 expressed on nonhematopoietic cells in halting expansion and proliferation of sdc1-deficient Tγδ17 cells. When subjected to imiquimod-induced psoriasiform dermatitis, Tγδ17 cells in sdc1KO mice displayed heightened responses accompanied by significantly increased skin inflammation than their wild-type counterparts. Furthermore, transferred sdc1-deficient γδ T cells caused more severe psoriasiform dermatitis than their sdc1-sufficient counterparts in TCRβδ KO hosts. The results uncover a novel role for sdc1 in controlling homeostasis of Tγδ17 cells and moderating host responses to psoriasis-like inflammation. The Journal of Immunology, 2018, 201: 1651-1661.

Original languageEnglish (US)
Pages (from-to)1651-1661
Number of pages11
JournalJournal of Immunology
Volume201
Issue number6
DOIs
StatePublished - Sep 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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