title: Interleukin-7 influences FOXP3+CD4+ regulatory T cells peripheral homeostasis.
abstract: Mechanisms governing peripheral CD4+ FOXP3+ regulatory T cells (Treg) survival and homeostasis are multiple suggesting tight and complex regulation of regulatory T cells homeostasis. Some specific factors, such as TGF-β, interleukin-2 (IL-2) and B7 costimulatory molecules have been identified as essentials for maintenance of the peripheral Treg compartment. Conversely, Treg dependency upon classical T cell homeostatic factors such as IL-7 is still unclear. In this work, we formally investigated the role of IL-7 in Treg homeostasis in vivo in murine models. We demonstrated that IL-7 availability regulated the size of peripheral Treg cell pool and thus paralleled the impact of IL-7 on conventional T cell pool. Moreover, we showed that IL-7 administration increased Treg cell numbers by inducing thymic-independent Treg peripheral expansion. Importantly the impact of IL-7 on Treg expansion was detected whether conventional T cells were present or absent as IL-7 directly participates to the peripheral expansion of Treg after adoptive transfer into lymphopenic hosts. Our results definitively identify IL-7 as a central factor contributing to Treg peripheral homeostasis, thus reassembling Treg to other T cell subsets in respect of their need for IL-7 for their peripheral maintenance.
authors.affiliation: INSERM, Le Kremlin-Bicêtre, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Simonetta
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gestermann
authors.forename: Kim Zita
authors.initials: KZ
authors.lastname: Martinet
authors.forename: Michele
authors.initials: M
authors.lastname: Boniotto
authors.forename: Pierre
authors.initials: P
authors.lastname: Tissières
authors.forename: Benedict
authors.initials: B
authors.lastname: Seddon
authors.forename: Christine
authors.initials: C
authors.lastname: Bourgeois
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D048429:Cell Size; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D007376:Interleukin-2 / Q000378:metabolism; D015851:Interleukin-7 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D008231:Lymphopenia / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015398:Signal Transduction / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000254:growth & development / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018398:Homeodomain Proteins; D007376:Interleukin-2; D015851:Interleukin-7; C064658:RAG-1 protein