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Foxp3-dependent and -independent functions of peripherally-induced Treg cells [09748]

UID: 10875

Author(s): van der Veeken, Joris*, Campbell, Clarissa M.*, Pritykin, Yury*, Schizas, Michail*, Hu, Wei*, Wang, Zhongmin*, Verter, Jacob G.*, Matheis, Fanny, Mucida, Daniel, Charbonnier, Louis-Marie, Chatila, Talal A., Rudensky, Alexander Y.* * MSK affiliated

Description
Summary from GEO:

"Regulatory T (Treg) cells expressing the lineage-defining transcription factor Foxp3 are essential for the maintenance of immune tolerance. Foxp3 expression can be induced in a subset of developing self-reactive thymocytes to yield thymic Treg (tTreg) cells, critical for tolerance against self-antigens. Alternatively, activation of mature naïve T cells under non-inflammatory conditions can drive the differentiation of peripherally-induced Treg (pTreg) cells, thought to contribute to tolerance against commensal microbes and dietary antigens. While Foxp3 is indispensable for tTreg cell development and function, its role in pTreg cells has remained unknown. Here, we used a genetic fate mapping approach to characterize polyclonal pTreg cells induced by microbial colonization. We found that expression of a pTreg cell-specific gene expression program was initiated in the mesenteric lymph node (mLN) in a Foxp3-independent manner. Moreover, in contrast to Treg cells in secondary lymphoid tissues, colonic microbiota-dependent pTreg cells did not depend on Foxp3 for their fitness or lineage commitment and were capable of suppressing colonic effector T cell expansion in a Foxp3-independent manner. Rather, Foxp3 was required in a cell-intrinsic manner to limit IL-17 production and to prevent the expansion of intestinal mast cells. Our results suggest that, extrathymic Foxp3 induction likely acts as a mechanism to fine-tune the activity of Th17-like cells with Foxp3-independent regulatory functions."

Overall design from GEO:

"RNA-seq analysis of DTR-GFP+ wild-type Treg cells and Thy1.1+ reporter-null+ cells from colonic lamina propria of Foxp3DTR-GFP/loxp-Thy1.1-STOP-loxp-GFP mice."
Subject of Study
Mus musculus
Subject(s)
Forkhead Transcription Factors
Immune Tolerance
T-Lymphocytes, Regulatory
Access via GEO


Accession #: GSE176236

Access via BioProject


Accession #: PRJNA735532

Access via SRA


Accession #: SRP322929

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA and BioProject databases provide open access to these files.
Associated Publications
van der Veeken J, Campbell C, Pritykin Y, Schizas M, Verter J, Hu W, Wang Z, Matheis F, Mucida D, Charbonnier L, Chatila T, Rudensky A. Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells. Immunity. 2022; 55(7):1173-1184.e7.
Equipment Used
Illumina HiSeq 4000

High throughput gene sequencing system

Dataset Format(s)
TXT
Dataset Size
252.2 KB
Data Catalog Record Updated
2023-10-04