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Obesity alters pathology and treatment response in inflammatory disease.
Bapat, Sagar P; Whitty, Caroline; Mowery, Cody T; Liang, Yuqiong; Yoo, Arum; Jiang, Zewen; Peters, Michael C; Zhang, Ling-Juan; Vogel, Ian; Zhou, Carmen; Nguyen, Vinh Q; Li, Zhongmei; Chang, Christina; Zhu, Wandi S; Hastie, Annette T; He, Helen; Ren, Xin; Qiu, Wenli; Gayer, Sarah G; Liu, Chang; Choi, Eun Jung; Fassett, Marlys; Cohen, Jarish N; Sturgill, Jamie L; Crotty Alexander, Laura E; Suh, Jae Myoung; Liddle, Christopher; Atkins, Annette R; Yu, Ruth T; Downes, Michael; Liu, Sihao; Nikolajczyk, Barbara S; Lee, In-Kyu; Guttman-Yassky, Emma; Ansel, K Mark; Woodruff, Prescott G; Fahy, John V; Sheppard, Dean; Gallo, Richard L; Ye, Chun Jimmie; Evans, Ronald M; Zheng, Ye; Marson, Alexander.
Afiliación
  • Bapat SP; NOMIS Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, USA. sagar.bapat@ucsf.edu.
  • Whitty C; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA. sagar.bapat@ucsf.edu.
  • Mowery CT; Medical Scientist Training Program, University of California, San Diego, La Jolla, CA, USA. sagar.bapat@ucsf.edu.
  • Liang Y; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA. sagar.bapat@ucsf.edu.
  • Yoo A; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA. sagar.bapat@ucsf.edu.
  • Jiang Z; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA. sagar.bapat@ucsf.edu.
  • Peters MC; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Zhang LJ; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Vogel I; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Zhou C; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Nguyen VQ; Medical Scientist Training Program, University of California, San Francisco, CA, USA.
  • Li Z; NOMIS Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Chang C; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Zhu WS; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Hastie AT; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • He H; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Ren X; Division of Pulmonary, Critical Care, Allergy and Sleep, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Qiu W; School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
  • Gayer SG; Department of Dermatology, University of California, San Diego, La Jolla, CA, USA.
  • Liu C; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Choi EJ; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Fassett M; NOMIS Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Cohen JN; Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Sturgill JL; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Crotty Alexander LE; NOMIS Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Suh JM; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Liddle C; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA.
  • Atkins AR; School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
  • Yu RT; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Downes M; Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Liu S; Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Nikolajczyk BS; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Lee IK; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Guttman-Yassky E; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Ansel KM; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
  • Woodruff PG; Department of Biomedical Science, Graduate School, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
  • Fahy JV; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Sheppard D; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA.
  • Gallo RL; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.
  • Ye CJ; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.
  • Evans RM; Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
  • Zheng Y; Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, USA.
  • Marson A; Pulmonary Critical Care Section, Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
Nature ; 604(7905): 337-342, 2022 04.
Article en En | MEDLINE | ID: mdl-35355021
ABSTRACT
Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and have led the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation. We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: PPAR gamma / Dermatitis Atópica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: PPAR gamma / Dermatitis Atópica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos