CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin

Mingcan Xia, Shaomin Hu, Yaoyao Fu, Wensen Jin, Qiyi Yi, Yurika Matsui, Jie Yang, Mary Ann McDowell, Surojit Sarkar, Vandana Kalia, Na Xiong

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background CCR10 and CCL27 make up the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases, including atopic dermatitis and psoriasis. This pair is thought to regulate the migration, maintenance, or both of skin T cells and is suggested to be therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive. Objective We sought to determine the expression and function of CCR10 in different subsets of skin T cells under both homeostatic and inflammatory conditions to gain a mechanistic insight into the potential roles of CCR10 during skin inflammation. Methods Using heterozygous and homozygous CCR10 knockout/enhanced green fluorescent protein knockin mice, we assessed the expression of CCR10 on regulatory and effector T cells of healthy and inflamed skin induced by chemicals, pathogens, and autoreactive T cells. In addition, we assessed the effect of CCR10 knockout on the maintenance and functions of different T cells and inflammatory status in the skin during different phases of the immune response. Results CCR10 expression is preferentially induced on memory-like skin-resident T cells and their progenitors for their maintenance in homeostatic skin but not expressed on most skin-infiltrating effector T cells during inflammation. In CCR10 knockout mice the imbalanced presence and dysregulated function of resident regulatory and effector T cells result in over-reactive and prolonged innate and memory responses in the skin, leading to increased clearance of Leishmania species infection in the skin. Conclusion CCR10 is a critical regulator of skin immune homeostasis.

Original languageEnglish (US)
Pages (from-to)634-644.e10
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number3
DOIs
StatePublished - Sep 2014
Externally publishedYes

Keywords

  • Chemokine receptor CCR10
  • Leishmania species
  • allergy
  • dermatitis
  • immune homeostasis
  • inflammation
  • maintenance
  • migration
  • regulatory T cells
  • skin infection
  • skin-resident T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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