A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response

• Ikebuchi, Ryoyo

• Teraguchi, Shunsuke

• Vandenbon, Alexis

• Honda, Tetsuya

• Shand, Francis H. W.

• Nakanishi, Yasutaka

• Watanabe, Takeshi

• Tomura, Michio

Abstract

Foxp3[+] regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing. Single-cell profiling revealed that CD43[+]CCR5[+] Tregs represented the main subset within the Il10/Gzmb-expressing cell population in the dLN. Moreover, CD43[+] CCR5[+] CXCR3[−] Tregs expressed skin-tropic chemokine receptors, were preferentially retained in inflamed skin and downregulated the cutaneous immune response. The identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses.

Journal

• Scientific Reports

  Scientific Reports 6 35002-, 2016-10-19

  Springer Nature

Keywords

• Acute inflammation
• Regulatory T cells

Details

• CRID: 1050001335843701888
• NII Article ID: 120006223629
• ISSN: 20452322
• DOI: 10.1038/srep35002
• HANDLE: 2433/219649
• Web Site: https://www.nature.com/articles/srep35002.pdf
• Web Site: https://www.nature.com/articles/srep35002
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN