PMID- 28134325 OWN - NLM STAT- MEDLINE DCOM- 20181024 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 DP - 2017 Jan 30 TI - Basophil-derived IL-6 regulates T(H)17 cell differentiation and CD4 T cell immunity. PG - 41744 LID - 10.1038/srep41744 [doi] LID - 41744 AB - Basophils are rare, circulating granulocytes proposed to be involved in T helper (T(H)) type 2 immunity, mainly through secretion of interleukin (IL)-4. In addition to IL-4, basophils produce IL-6 and tumor necrosis factor (TNF)-alpha in response to immunoglobulin E (IgE) crosslinking. Differentiation of T(H)17 cells requires IL-6 and transforming growth factor (TGF)-beta, but whether basophils play a significant role in T(H)17 induction is unknown. Here we show a role for basophils in T(H)17 cell development by using in vitro T cell differentiation and in vivo T(H)17-mediated inflammation models. Bone marrow derived-basophils (BMBs) and splenic basophils produce significant amounts of IL-6 as well as IL-4 following stimulation with IgE crosslink or cholera toxin (CT). In addition, through IL-6 secretion, BMBs cooperate with dendritic cells to promote T(H)17 cell differentiation. In the T(H)17 lung inflammation model, basophils are recruited to the inflamed lungs following CT challenge, and T(H)17 responses are significantly reduced in the absence of basophils or IL-6. Furthermore, reconstitution with wild-type, but not IL-6-deficient, basophils restored CT-mediated lung inflammation. Lastly, basophil-deficient mice showed reduced phenotypes of T(H)17-dependent experimental autoimmune encephalomyelitis. Therefore, our results indicate that basophils are an important inducer of T(H)17 cell differentiation, which is dependent on IL-6 secretion. FAU - Yuk, Chae Min AU - Yuk CM AD - Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea. AD - Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute for the Bio-Century, KAIST, Daejeon, 34141, Korea. FAU - Park, Hyeung Ju AU - Park HJ AD - Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea. AD - Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute for the Bio-Century, KAIST, Daejeon, 34141, Korea. FAU - Kwon, Bo-In AU - Kwon BI AD - K-herb Research Center, Korea Institute of Oriental Medicine (KIOM), Daejeon, 34054, Korea. FAU - Lah, Sang Joon AU - Lah SJ AD - Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea. AD - Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute for the Bio-Century, KAIST, Daejeon, 34141, Korea. FAU - Chang, Jun AU - Chang J AD - Division of Life and Pharmaceutical Science, Ewha Womans University, Seoul, 03760, Korea. FAU - Kim, Ji-Young AU - Kim JY AD - Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, Korea. FAU - Lee, Kyung-Mi AU - Lee KM AD - Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 02841, Korea. FAU - Park, Su-Hyung AU - Park SH AD - Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea. AD - Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute for the Bio-Century, KAIST, Daejeon, 34141, Korea. FAU - Hong, Seokchan AU - Hong S AD - Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute for the Bio-Century, KAIST, Daejeon, 34141, Korea. AD - Division of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, Korea. FAU - Lee, Seung-Hyo AU - Lee SH AD - Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea. AD - Graduate School of Medical Science and Engineering (GSMSE), Biomedical Research Center, KAIST Institute for the Bio-Century, KAIST, Daejeon, 34141, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170130 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - 9012-63-9 (Cholera Toxin) SB - IM MH - Animals MH - Basophils/*immunology/*metabolism MH - Biomarkers MH - CD4-Positive T-Lymphocytes/*cytology/*physiology MH - Cell Differentiation/*immunology MH - Cholera Toxin/adverse effects MH - Cytokines/biosynthesis MH - Disease Models, Animal MH - Immunity MH - Immunophenotyping MH - Inflammation/etiology/metabolism/pathology MH - Interleukin-6/deficiency/*metabolism MH - Mice MH - Mice, Knockout MH - Th17 Cells/*cytology/*physiology PMC - PMC5278410 COIS- The authors declare no competing financial interests. EDAT- 2017/01/31 06:00 MHDA- 2018/10/26 06:00 PMCR- 2017/01/30 CRDT- 2017/01/31 06:00 PHST- 2016/09/20 00:00 [received] PHST- 2016/12/28 00:00 [accepted] PHST- 2017/01/31 06:00 [entrez] PHST- 2017/01/31 06:00 [pubmed] PHST- 2018/10/26 06:00 [medline] PHST- 2017/01/30 00:00 [pmc-release] AID - srep41744 [pii] AID - 10.1038/srep41744 [doi] PST - epublish SO - Sci Rep. 2017 Jan 30;7:41744. doi: 10.1038/srep41744.