期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 31, 页码 E6400-E6409出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1705551114
关键词
Treg cell; T-follicular regulatory cell; Tfr cell; germinal center; Tfh cell
资金
- Japan Society for the Promotion of Science (JSPS) [26253030, 16H05181]
- JSPS [15K19129]
- Novartis Foundation (Japan) for the Promotion of Science [15-123]
- Japan Agency for Medical Research and Development [16ak0101010h0205]
- Grants-in-Aid for Scientific Research [15K19129, 17K08882, 16H05181, 16K15289, 15H04744] Funding Source: KAKEN
T-follicular helper (Tfh) cells differentiate through a multistep process, culminating in germinal center (GC) localized GC-Tfh cells that provide support to GC-B cells. T-follicular regulatory (Tfr) cells have critical roles in the control of Tfh cells and GC formation. Although Tfh-cell differentiation is inhibited by IL-2, regulatory T (Treg) cell differentiation and survival depend on it. Here, we describe a CD25(-) subpopulation within both murine and human PD1(+)CXCR5(+)Foxp3(+) Tfr cells. It is preferentially located in the GC and can be clearly differentiated from CD25(+) non-GC-Tfr, Tfh, and effector Treg (eTreg) cells by the expression of a wide range of molecules. In comparison to CD25(+) Tfr and eTreg cells, CD25(-) Tfr cells partially down-regulate IL-2-dependent canonical Treg features, but retain suppressive function, while simultaneously upregulating genes associated with Tfh and GC-Tfh cells. We suggest that, similar to Tfh cells, Tfr cells follow a differentiation pathway generating a mature GC-localized subpopulation, CD25(-) Tfr cells.
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