title: STAT3-dependent IL-21 production from T helper cells regulates hematopoietic progenitor cell homeostasis.
abstract: The contribution of specific cell types to the production of cytokines that regulate hematopoiesis is still not well defined. We have previously identified T cell-dependent regulation of hematopoietic progenitor cell (HPC) numbers and cycling. In this report, we demonstrated that HPC activity is decreased in mice with STAT3-deficient T cells, a phenotype that is not because of decreased expression of IL-17 or RORγt. STAT3 expression in T cells was required for IL-21 production by multiple T helper subsets, and neutralization of IL-21 resulted in decreased HPC activity identical to that in mice with STAT3-deficient T cells. Importantly, injection of IL-21 rescued HPC activity in mice with STAT3-deficient T cells. Thus, STAT3-dependent IL-21 production in T cells is required for HPC homeostasis.
authors.affiliation: Department of Microbiology, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. mkaplan2@iupui.edu
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glosson
authors.forename: Gretta L
authors.initials: GL
authors.lastname: Stritesky
authors.forename: Norman
authors.initials: N
authors.lastname: Yeh
authors.forename: John
authors.initials: J
authors.lastname: Kinzfogl
authors.forename: Sara L
authors.initials: SL
authors.lastname: Rohrabaugh
authors.forename: Ritobrata
authors.initials: R
authors.lastname: Goswami
authors.forename: Duy
authors.initials: D
authors.lastname: Pham
authors.forename: David E
authors.initials: DE
authors.lastname: Levy
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
authors.forename: Scott
authors.initials: S
authors.lastname: Cooper
authors.forename: Giao
authors.initials: G
authors.lastname: Hangoc
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D000098546:Interleukin-21