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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Epidermis / metabolism
  • Female
  • Gene Deletion
  • Humans
  • Inflammation / pathology
  • Interleukin-17 / biosynthesis*
  • Interleukin-23 / metabolism
  • Lymphocyte Activation / immunology
  • Male
  • Mice, Inbred C57BL
  • Microbiota*
  • Neoplasm Proteins / deficiency
  • Neoplasm Proteins / metabolism*
  • Organ Specificity
  • Psoriasis / immunology
  • Psoriasis / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Skin / immunology*
  • Skin / pathology
  • Th17 Cells / metabolism*

Substances

  • Antigens, CD
  • CD109 protein, mouse
  • Interleukin-17
  • Interleukin-23
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell, gamma-delta

Grant support