title: Gut-Specific Delivery of T-Helper 17 Cells Reduces Obesity and Insulin Resistance in Mice.
abstract: Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4+T-helper (TH) cells with obesity and the effects of gut-tropic TH17 cells in mice on a high-fat diet (HFD).
  
  
  
  We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry. Mice fed a vitamin A-deficient HFD were compared with mice fed a vitamin A-sufficient HFD. Obese RAG1-deficient mice were given injections of only regulatory T cells or a combination of regulatory T cells and TH17 cells (wild type or deficient in integrin β7 subunit or interleukin 17 [IL17]). Mice were examined for weight gain, fat mass, fatty liver, glucose tolerance, and insulin resistance. Fecal samples were collected before and after T cell transfer and analyzed for microbiota composition by metagenomic DNA sequencing and quantitative polymerase chain reaction.
  
  
  
  Mice placed on a HFD became obese, which affected the distribution of small intestinal CD4+THcells. Intestinal tissues from obese mice had significant reductions in the proportion of TH17 cells but increased proportion of TH1 cells, compared with intestinal tissues from nonobese mice. Depletion of vitamin A in obese mice further reduced the proportion of TH17 cells in small intestine; this reduction correlated with more weight gain and worsening of glucose intolerance and insulin resistance. Adoptive transfer of in vitro-differentiated gut-tropic TH17 cells to obese mice reduced these metabolic defects, which required the integrin β7 subunit and IL17. Delivery of TH17 cells to intestines of mice led to expansion of commensal microbes associated with leanness.
  
  
  
  In mice, intestinal TH17 cells contribute to development of a microbiota that maintains metabolic homeostasis, via IL17. Gut-homing TH17 cells might be used to reduce metabolic disorders in obese individuals.
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea; Department of Microbiology, Graduate School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Chun-Pyo
authors.initials: CP
authors.lastname: Hong
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Park
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea.
authors.forename: Bo-Gie
authors.initials: BG
authors.lastname: Yang
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Department of Systems Biology and Division of Life Sciences, Yonsei University, Seoul, Republic of Korea; Biosystems and Bioengineering Program, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwak
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Gil-Woo
authors.initials: GW
authors.lastname: Lee
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Min Seong
authors.initials: MS
authors.lastname: Jang
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Jeun
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Gihoon
authors.initials: G
authors.lastname: You
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea.
authors.forename: Kwang Soon
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Youngwoo
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Ji-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, Republic of Korea; Center for Plant Aging Research, Institute for Basic Science, Daegu, Republic of Korea.
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Sin-Hyeog
authors.initials: SH
authors.lastname: Im
authors.affiliation: Department of Systems Biology and Division of Life Sciences, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jihyun F
authors.initials: JF
authors.lastname: Kim
authors.affiliation: Research Institute, MD Healthcare, Seoul, Republic of Korea.
authors.forename: Yoon-Keun
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Seoh
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Republic of Korea; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea. Electronic address: youmekim@postech.ac.kr.
authors.forename: You-Me
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan. Electronic address: jang@ifrec.osaka-u.ac.jp.
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D018928:Immunity, Mucosal; D007333:Insulin Resistance; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D010641:Phenotype; D058504:Th17 Cells / Q000276:immunology / Q000382:microbiology / Q000637:transplantation*; D013997:Time Factors; D014802:Vitamin A Deficiency / Q000150:complications
chemical_list: D018398:Homeodomain Proteins; D039641:Integrin beta Chains; D020381:Interleukin-17; C091368:integrin beta7; C064658:RAG-1 protein
keywords: Glucose Tolerance; Intestinal Microbiota; Mucosal Immunity