Group 2 innate lymphoid cells (ILC2s) play crucial roles in maintaining adipose tissue homeostasis. Recent studies indicate that ILC2s are dysregulated in obesity. However, the regulatory mechanisms governing adipose tissue ILC2 function remain inadequately explored. In this study, we demonstrated that mechanistic target of rapamycin complex 1 (mTORC1) activity is impaired in adipose tissue ILC2s from obese mice and humans. Deletion of Raptor, a critical adaptor protein in mTORC1, results in reduced numbers of ILC2s and diminished type 2 cytokine production in ILC2s, leading to increased adipose tissue inflammation and insulin resistance. Mechanistically, mTORC1 signaling upregulates PPAR gamma expression through HIF-1 alpha, which promotes mitochondrial biogenesis and ST2 expression to sustain ILC2 metabolic and functional fitness. Together, our data identify mTORC1 as a crucial regulator that coordinates adipose tissue ILC2 metabolic and immunological homeostasis and prevents obesity-associated insulin resistance.
[1]Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Ctr Immune Related Dis,Shanghai Inst Immunol, Shanghai, Peoples R China.
[2]Shanghai Jiao Tong Univ, Chinese Minist Educ, Key Lab Cell Differentiat & Apoptosis, Sch Med,Dept Immunol & Microbiol, Shanghai, Peoples R China.
[3]Shanghai Jiao Tong Univ, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai Inst Immunol, Sch Med,Dept Immunol & Microbiol, Shanghai, Peoples R China.
[4]Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai, Peoples R China.
[5]Nanjing Univ, Drum Tower Hosp, Branch Natl Clin Res Ctr Metab Dis, Dept Endocrinol,Med Sch, Nanjing, Peoples R China.
[6]Hainan Med Univ, Hainan Acad Med Sci, Hainan, Peoples R China.
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