TCR Transgenic Mice Reveal Stepwise, Multi-site Acquisition of the Distinctive Fat-Treg Phenotype.
Cell, 2018/07/12;174(2):285-299.e12.
Li C[1], DiSpirito JR[1], Zemmour D[1], Spallanzani RG[1], Kuswanto W[1], Benoist C[1], Mathis D[2]
Affiliations
PMID: 29887374DOI: 10.1016/j.cell.2018.05.004
Impact factor: 66.85
Abstract
Visceral adipose tissue (VAT) hosts a population of regulatory T (Treg) cells, with a unique phenotype, that controls local and systemic inflammation and metabolism. Generation of a T cell receptor transgenic mouse line, wherein VAT Tregs are highly enriched, facilitated study of their provenance, dependencies, and activities. We definitively established a role for T cell receptor specificity, uncovered an unexpected function for the primordial Treg transcription-factor, Foxp3, evidenced a cell-intrinsic role for interleukin-33 receptor, and ordered these dependencies within a coherent scenario. Genesis of the VAT-Treg phenotype entailed a priming step in the spleen, permitting them to exit the lymphoid organs and surveil nonlymphoid tissues, and a final diversification process within VAT, in response to microenvironmental cues. Understanding the principles of tissue-Treg biology is a prerequisite for precision-targeting strategies.
Keywords: Foxp3; IL-33; PPARγ; TCR transgenic mice; adipose tissue; immunometabolism; immunoregulation; regulatory T cell
MeSH terms
Animals; Chromatin Assembly and Disassembly; Forkhead Transcription Factors; Interleukin-1 Receptor-Like 1 Protein; Intra-Abdominal Fat; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; PPAR gamma; Phenotype; RNA; Receptors, Antigen, T-Cell; Receptors, Interleukin; Single-Cell Analysis; Spleen; T-Lymphocytes, Regulatory; Transcriptome
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