title: IL-21 inhibits IL-17A-producing γδ T-cell response after infection with Bacillus Calmette-Guérin via induction of apoptosis.
abstract: Innate γδ T cells expressing Vγ6 produce IL-17A at an early stage following infection with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In this study, we used IL-21 receptor knockout (IL-21R KO) mice and IL-21-producing recombinant BCG mice (rBCG-Ag85B-IL-21) to examine the role of IL-21 in the regulation of IL-17A-producing innate γδ T-cell response following BCG infection. IL-17A-producing Vγ6+γδ T cells increased in the peritoneal cavity of IL-21R KO mice more than in wild type mice after BCG infection. In contrast, the number of IL-17A-producing Vγ6+γδ T cells was significantly lower after inoculation with rBCG-Ag85B-IL-21 compared with control rBCG-Ag85B. Notably, exogenous IL-21 selectively induced apoptosis of IL-17A-producing Vγ6+γδ T cells via Bim. Thus, these results suggest that IL-21 acts as a potent inhibitor of a IL-17A-producing γδ T-cell subset during BCG infection.
authors.affiliation: 1 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.|2 Beijing Key Laboratory of Drug Resistance Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China.
authors.forename: Yinxia
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 1 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: 1 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hatano
authors.affiliation: 1 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Noguchi
authors.affiliation: 1 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Tesshin
authors.initials: T
authors.lastname: Murakami
authors.affiliation: 3 Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: 4 Department of Immunology, China Medical University, Shenyang, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: 5 Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohara
authors.affiliation: 1 Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D000818:Animals; D017209:Apoptosis; D001500:BCG Vaccine / Q000276:immunology*; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology*; D010529:Peritoneal Cavity / Q000382:microbiology / Q000473:pathology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology; D000098546:Interleukin-21
chemical_list: D001500:BCG Vaccine; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D020381:Interleukin-17; D007378:Interleukins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053655:Receptors, Interleukin-21; C000589613:T-cell receptor Vgamma6, mouse; D000098546:Interleukin-21
keywords: BCG; IL-17A; IL-21; apoptosis; γδ T cells