title: Donor- but not host-derived interleukin-10 contributes to the regulation of experimental graft-versus-host disease.
abstract: IL-10 is a key immune-regulatory cytokine, and its gene polymorphisms correlate with severity of clinical GVHD. IL-10 is made by a variety of donor and host cells, but the functional relevance of its source and its role in the biology of acute GVHD are not well understood. We used preclinical models to examine the relevance of IL-10(-/-) in donor and host cellular subsets on the severity of GVHD. IL-10(-/-) in host tissues or in the donor grafts did not alter donor Teff-mediated severity of GVHD. Furthermore, neither host-derived nor donor Teff-derived IL-10 was required for regulation of GVHD by WT CD4(+)CD25(+) donor Tregs. By contrast, Treg-derived IL-10, although not obligatory, was necessary for optimal reduction of GVHD by mature donor Tregs. Importantly, IL-10 from donor BM grafts was also critical for optimal donor Treg-mediated suppression of GVHD. Together, these data suggest that IL-10 does not contribute to the induction of GVHD severity by the Teffs. However, donor BM graft and Treg-derived IL-10 are important for donor Treg-mediated suppression of GVHD.
authors.affiliation: Department of Internal Medicine and University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
authors.forename: Isao
authors.initials: I
authors.lastname: Tawara
authors.forename: Yaping
authors.initials: Y
authors.lastname: Sun
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Tomomi
authors.initials: T
authors.lastname: Toubai
authors.forename: Evelyn
authors.initials: E
authors.lastname: Nieves
authors.forename: Rebecca
authors.initials: R
authors.lastname: Evers
authors.forename: Mariem
authors.initials: M
authors.lastname: Alrubaie
authors.forename: Nathan
authors.initials: N
authors.lastname: Mathewson
authors.forename: Hiroya
authors.initials: H
authors.lastname: Tamaki
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: C556062:IL10 protein, mouse; D016753:Interleukin-10