title: Interleukin-15 Constrains Mucosal T Helper 17 Cell Generation: Influence of Mononuclear Phagocytes.
abstract: Interleukin (IL)-15 has multiple roles in innate and adaptive immunity, especially regarding CD8+ T cells and natural killer cells. However, the role of IL-15 in regulating differentiation of T helper cell subsets and mononuclear phagocytes (MPs) in different tissues in vivo is unknown. Here we report that IL-15 indirectly regulates Th17 but not other Th subsets in the intestinal lamina propria (LP), apparently through effects on MPs. Th17 cells in the LP were more prevalent in IL-15 KO mice than their wild-type counterparts, and less prevalent in IL-15 transgenic mice than their wild-type littermates, even co-caged. MPs from the LP of these mice were sufficient to mimic the in vivo finding in vitro by skewing of cocultured wild type OVA-specific CD4+ T cells. However, production of IL-15 or lack thereof by these MPs was not sufficient to explain the skewing, as addition or blockade of IL-15 in the cultures had no effect. Rather, a skewing of the relative proportion of CD11b+, CD103+ and double positive LP MP subsets in transgenic and KO could explain the differences in Th17 cells. Thus, IL-15 may influence MP subsets in the gut in a novel way that alters the frequency of LP Th17 cells.
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Yu
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Blake
authors.initials: B
authors.lastname: Frey
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Jay
authors.initials: J
authors.lastname: Berzofsky
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D019409:Interleukin-15 / Q000172:deficiency / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010586:Phagocytes / Q000166:cytology*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D000941:Antigens; D019409:Interleukin-15; D020381:Interleukin-17