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bioRxiv · 10.1101/589994

The transcriptional regulator Id2 is critical for adipose-resident regulatory T cell differentiation, survival and function

Frias, A. B.·Hyzny, E. J.·Buechel, H. M.·Beppu, L.·Xie, B.·Jurczak, M. J.·D'Cruz, L. M.
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Abstract

Adipose regulatory T cells (aTregs) have emerged as critical cells for the control of local and systemic inflammation. In this study, we show a distinctive role for the transcriptional regulator Id2 in the differentiation, survival and function of aTregs. Id2 was highly expressed in aTregs compared with high Id3 expression in lymphoid Tregs. Treg-specific deletion of Id2 resulted in a substantial decrease in aTregs, while Tregs in the spleen and lymph nodes were unaffected. Additionally, loss of Id2 resulted in decreased expression of aTreg associated markers including ST2, CCR2, KLRG1 and GATA3. Gene expression analysis revealed that Id2 expression was essential for the survival of aTregs and loss of Id2 increased cell death in aTregs due to increased Fas expression. Id2-mediated aTreg depletion resulted in increased systemic inflammation, increased inflammatory macrophages and CD8+ effector T cells and loss of glucose tolerance under standard diet conditions. Thus, we reveal an unexpected and novel function for Id2 in mediating differentiation, survival and function of adipose-resident Tregs, that when lost resulting in increased metabolic perturbation.

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Frias, A. B., Hyzny, E. J., Buechel, H. M., Beppu, L., Xie, B., Jurczak, M. J., D'Cruz, L. M.. 2019-03-27. The transcriptional regulator Id2 is critical for adipose-resident regulatory T cell differentiation, survival and function. https://doi.org/10.1101/589994

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