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- Title
TCF-1 negatively regulates the suppressive ability of canonical and noncanonical Tregs.
- Authors
Mammadli, Mahinbanu; Suo, Liye; Sen, Jyoti Misra; Karimi, Mobin
- Abstract
Regulatory T cells are suppressive immune cells used in various clinical and therapeutic applications. Canonical regulatory T cells express CD4, FOXP3, and CD25, which are considered definitive markers of their regulatory T-cell status when expressed together. However, a subset of noncanonical regulatory T cells expressing only CD4 and FOXP3 have recently been described in some infection contexts. Using a unique mouse model for the first time demonstrated that the TCF-1 regulation of regulatory T-cell suppressive function is not limited to the thymus during development. Our data showed that TCF-1 also regulated regulatory T cells' suppressive ability in secondary organs and graft-vs-host disease target organs as well as upregulating noncanonical regulatory T cells. Our data demonstrated that TCF-1 regulates the suppressive function of regulatory T cells through critical molecules like GITR and PD-1, specifically by means of noncanonical regulatory T cells. Our in vitro approaches show that TCF-1 regulates the regulatory T-cell effector-phenotype and the molecules critical for regulatory T-cell migration to the site of inflammation. Using in vivo models, we show that both canonical and noncanonical regulatory T cells from TCF-1 cKO mice have a superior suppressive function, as shown by their ability to control conventional T-cell proliferation, avert acute graft-vs-host disease, and limit tissue damage. Thus, for the first time, we provide evidence that TCF-1 negatively regulates the suppressive ability of canonical and noncanonical regulatory T cells. These findings provide evidence that TCF-1 is a novel target for developing strategies to treat alloimmune disorders.
- Subjects
REGULATORY T cells; T cells; CD25 antigen
- Publication
Journal of Leukocyte Biology, 2023, Vol 113, Issue 5, p489
- ISSN
0741-5400
- Publication type
Article
- DOI
10.1093/jleuko/qiad019