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bioRxiv · 10.1101/359687

Dynamic expression of Id3 defines the stepwise differentiation of tissue-resident regulatory T cells

Sullivan, J. M.·Hollbacher, B.·Campbell, D.
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Abstract

Foxp3+ regulatory T (TR) cells are phenotypically and functionally diverse, and broadly distributed in lymphoid and non-lymphoid tissues. However, the pathways guiding the differentiation of tissue-resident TR populations have not been well defined. By regulating E-protein function, Id3 controls the differentiation of CD8+ effector T cells and is essential for TR maintenance and function. We show that dynamic expression of Id3 helps define three distinct TR populations, Id3+CD62LhiCD44lo central (c)TR, Id3+CD62LloCD44hi effector (e)TR and Id3- eTR. Adoptive transfer experiments and transcriptome analyses support a stepwise model of differentiation from Id3+ cTR to Id3+ eTR to Id3- eTR. Furthermore, Id3- eTR have high expression of functional inhibitory markers and a transcriptional signature of tissue-resident TR. Accordingl Id3- eTR are highly enriched in non-lymphoid organs, but virtually absent from blood and lymph Thus, we propose that tissue-resident TR develop in a multi-step process associated with Id3 downregulation.

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Sullivan, J. M., Hollbacher, B., Campbell, D.. 2018-06-30. Dynamic expression of Id3 defines the stepwise differentiation of tissue-resident regulatory T cells. https://doi.org/10.1101/359687

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