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IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion.

M. Catálfamo,M. Catálfamo,Cécile Le Saout,Megan A. Luckey,A. Villarino,Mindy Smith,Rebecca B. Hasley,T. Myers,H. Imamichi,Jung-Hyun Park,J. O’Shea,H. Lane

Published 2017 in JCI Insight

ABSTRACT

IL-7 regulates homeostatic mechanisms that maintain the overall size of the T cell pool throughout life. We show that, under steady-state conditions, IL-7 signaling is principally mediated by activation of signal transducers and activators of transcription 5 (STAT5). In contrast, under lymphopenic conditions, there is a modulation of STAT1 expression resulting in an IL-7-dependent STAT1 and STAT5 activation. Consequently, the IL-7-induced transcriptome is altered with enrichment of IFN-stimulated genes (ISGs). Moreover, STAT1 overexpression was associated with reduced survival in CD4+ T cells undergoing lymphopenia-induced proliferation (LIP). We propose a model in which T cells undergoing LIP upregulate STAT1 protein, "switching on" an alternate IL-7-dependent program. This mechanism could be a physiological process to regulate the expansion and size of the CD4+ T cell pool. During HIV infection, the virus could exploit this pathway, leading to the homeostatic dysregulation of the T cell pools observed in these patients.

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