研究課題
Regulatory T-cells (Tregs) were initially identified by their expression of the IL-2 receptor CD25 and later by the transcription factor Foxp3. A subgroup of Treg, T-follicular regulatory (Tfr) cells are believe to be critical to the control of T-follicular helper cells (Tfh) and resulting germinal centre B-cell antibody responses. However, we do not understand the biology of Tfr cells well. This project set out to better understand the role of Tfr in autoimmunity.We made the important finding that mature Tfr cells downregulate CD25 expression and form a subgroup of CD25lo Tfr that preferentially locate in the germinal centres. Tfr lose CD25 expression in order to upregulate the Tfh associated transcription factor BCL6 which is otherwise inhibited by IL-2 signalling via CD25. This loss of dependence on IL-2 makes Tfr unique among the otherwise IL-2 dependent group of Tregs. We found that these CD25lo Tfr are present in both mice and also human blood and tonsils. We characterised human Tregs and find that up to 30% are CXCR5+CD25lo Tfr. Despite loss of CD25 Tfr retain expression of Foxp3 and other critical Treg molecules such as CTLA-4. These findings are a significant step towards our understanding of Tfr biology and also have wider implications since many treatments currently investigated in human clinical trials rely on either manipulation of IL-2 availability or depletion of Tregs via anti-CD25 antibodies.The resulting paper is currently under review.
すべて 2017 2016
すべて 雑誌論文 (3件) (うち国際共著 3件、 査読あり 3件、 謝辞記載あり 1件、 オープンアクセス 1件) 学会発表 (1件) (うち国際学会 1件) 図書 (1件)
Cell Reports
巻: 18 ページ: 906-916
10.1016/j.celrep.2017.01.067
PLOS one
巻: 11 ページ: -
10.1371/journal.pone.0162306
Stem Cells Dev
巻: 25 ページ: 774-87
10.1089/scd.2016.0009
