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Cell Rep. 2019 Oct 8;29(2):391-405.e5. doi: 10.1016/j.celrep.2019.09.003.

CD109 Restrains Activation of Cutaneous IL-17-Producing γδ T Cells by Commensal Microbiota.

Author information

1
Meakins-Christie Laboratories, Department of Microbiology and Immunology, McGill University Health Centre Research Institute, Montreal, QC, Canada.
2
CHU de Québec-Université Laval, Hôpital de l'Enfant-Jésus, Québec, QC, Canada.
3
Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre Research Institute, Montreal, QC, Canada.
4
Infectious Disease Susceptibility Program, McGill University Health Centre (MUHC) and Research Institute-MUHC (RI-MUHC), Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada.
5
Meakins-Christie Laboratories, Department of Microbiology and Immunology, McGill University Health Centre Research Institute, Montreal, QC, Canada; Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre Research Institute, Montreal, QC, Canada. Electronic address: irah.king@mcgill.ca.

Abstract

Interleukin-17-producing γδ T (γδ17) cells play a central role in protective and pathogenic immune responses. However, the tissue-specific mechanisms that control the activation of these innate lymphocytes are not known. Here, we demonstrate that CD109, a glycosylphosphatidylinositol (GPI)-anchored protein highly expressed by keratinocytes, is an important regulator of skin homeostasis and γδ17 cell activation. Genetic deletion of CD109 results in spontaneous epidermal hyperplasia, aberrant accumulation of dermal-derived γδ17 cells, and enhanced susceptibility to psoriasiform inflammation. In this context, γδ17 activation requires interleukin (IL)-23 signals and is reversed by transient depletion of the skin microbiota. Mechanistically, CD109 restrains γδ17 cell activation in a cell-extrinsic manner by fortifying skin barrier integrity. Collectively, our data provide insight into the regulation of the skin IL-23/IL-17 immune axis and how homeostasis is maintained at this important barrier site.

KEYWORDS:

CD109; IL-17; barrier tissue; gamma delta T cells; immunity; microbiota; psoriasis; skin

PMID:
31597099
DOI:
10.1016/j.celrep.2019.09.003
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