Obesity disrupts ILC2 metabolic and functional homeostasis by inhibiting mTORC1 signaling

Obesity disrupts ILC2 metabolic and functional homeostasis by inhibiting mTORC1 signaling

  • Czech MP. Insulin action and resistance in obesity and type 2 diabetes. Nat Med. 2017;23:804–14.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Powell-Wiley TM, Poirier P, Burke LE, Després J-P, Gordon-Larsen P, Lavie CJ, et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2021;143:e984–e1010.

  • Stefan N, Cusi K. A global view of the interplay between nonalcoholic fatty liver disease and diabetes. Lancet Diab Endocrinol. 2022;10:284–96.

    Article 

    Google Scholar
     

  • Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219–46.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15:930–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15:914–20.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ji Z, Wu S, Xu Y, Qi J, Su X, Shen L. Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration. Front Immunol. 2019;10:1881.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang H, Shen L, Sun X, Liu F, Feng W, Jiang C, et al. Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity. Nat Commun. 2019;10:3254.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sun J, Zhang Y, Zhang Q, Hu L, Zhao L, Wang H, et al. Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance. Immunity. 2024;57:1289–305.e9.

  • McLaughlin T, Ackerman SE, Shen L & Engleman E. Role of innate and adaptive immunity in obesity-associated metabolic disease. J Clin Invest. 2017;127:5–13.

  • Shen L, Chng MHY, Alonso MN, Yuan R, Winer DA, Engleman EG. B-1a lymphocytes attenuate insulin resistance. Diabetes. 2015;64:593–603.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17:610–7.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang J, Qiu J, Zhou W, Cao J, Hu X, Mi W, et al. Neuropilin-1 mediates lung tissue-specific control of ILC2 function in type 2 immunity. Nat Immunol. 2022;23:237–50.

    Article 
    PubMed 

    Google Scholar
     

  • Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA, Sonnenberg GF, et al. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature. 2015;519:242–6.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Oldenhove G, Boucquey E, Taquin A, Acolty V, Bonetti L, Ryffel B, et al. PD-1 is involved in the dysregulation of type 2 innate lymphoid cells in a murine model of obesity. Cell Rep. 2018;25:2053–60.e4.

  • Hildreth AD, Ma F, Wong YY, Sun R, Pellegrini M, O’Sullivan TE. Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat Immunol. 2021;22:639–53.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Flach M, Diefenbach A. Adipose tissue: ILC2 crank up the heat. Cell Metab. 2015;21:152–3.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee M-W, Odegaard JustinI, Mukundan L, Qiu Y, Molofsky AriB, Nussbaum JesseC, et al. Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Cell. 2015;160:74–87.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ben-Sahra I, Manning BD. mTORC1 signaling and the metabolic control of cell growth. Curr Opin Cell Biol. 2017;45:72–82.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang H, Long L, Zhou P, Chapman NM, Chi H. mTOR signaling at the crossroads of environmental signals and T-cell fate decisions. Immunol Rev. 2020;295:15–38.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang J, Yang L, Guan F, Miller H, Camara NOS, James LK, et al. The role of Raptor in lymphocytes differentiation and function. Front Immunol. 2023;14:1146628.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang K, Shrestha S, Zeng H, Karmaus PWF, Neale G, Vogel P, et al. T-cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming. Immunity. 2013;39:1043–56.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Salmond RJ, Mirchandani AS, Besnard AG, Bain CC, Thomson NC, Liew FY. IL-33 induces innate lymphoid cell-mediated airway inflammation by activating mammalian target of rapamycin. J Allergy Clin Immunol. 2012;130:1159–66.e6.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Surace LA-O, Doisne JA-O, Croft CA-O, Thaller A, Escoll PA-OX, Marie S, et al. Dichotomous metabolic networks govern human ILC2 proliferation and function. Nat Immunol. 2021;22:1367–74.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Galbraith LCA, Mui E, Nixon C, Hedley A, Strachan D, MacKay G, et al. PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer. Oncogene. 2021;40:2355–66.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Karagiannis F, Masouleh SK, Wunderling K, Surendar J, Schmitt V, Kazakov A, et al. Lipid-droplet formation drives pathogenic group 2 innate lymphoid cells in airway inflammation. Immunity. 2020;52:885.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xiao Q, He J, Lei A, Xu H, Zhang L, Zhou P, et al. PPARγ enhances ILC2 function during allergic airway inflammation via transcription regulation of ST2. Mucosal Immunol. 2021;14:468–78.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fali T, Aychek T, Ferhat M, Jouzeau J-Y, Busslinger M, Moulin D, et al. Metabolic regulation by PPARγ is required for IL-33-mediated activation of ILC2s in lung and adipose tissue. Mucosal Immunol. 2021;14:585–93.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cho HY, Gladwell W, Wang X, Chorley B, Bell D, Reddy SP Wang X, Wang X, Fau -, et al. Nrf2-regulated PPAR{gamma} expression is critical to protection against acute lung injury in mice. Am J Respir Crit Care Med. 2010;182:170–82.

  • Zhan L, Zhang H, Zhang Q, Woods CG, Chen Y, Xue P, et al. Regulatory role of KEAP1 and NRF2 in PPARγ expression and chemoresistance in human non-small cell lung carcinoma cells. Free Radic Biol Med. 2012;53:758–68.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li YA-O, Lu YA-O, Lin SH, Li N, Han YA-O, Huang Q, et al. Insulin signaling establishes a developmental trajectory of adipose regulatory T cells. Nat Immunol. 2021;22:1175–85.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen Y, He R, Han Z, Wu Y, Wang Q, Zhu X, et al. Cooperation of ATF4 and CTCF promotes adipogenesis through transcriptional regulation. Cell Biol Toxicol. 2022;38:741–63.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Morita M, Gravel S-P, Chénard V, Sikström K, Zheng L, Alain T, et al. mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab. 2013;18:698–711.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007;450:736–40.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sun L, Ji S, Xie X, Si L, Liu S, Lin Y, et al. Deciphering the interaction between Twist1 and PPARγ during adipocyte differentiation. Cell Death Dis. 2023;14:764.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aprile M, Cataldi S, Ambrosio MR, D’Esposito V, Lim K, Dietrich A, et al. PPARγΔ5, a naturally, occurring dominant-negative splice isoform, impairs PPARγ function and adipocyte differentiation. Cell Rep. 2018;25:1577–92.e6.

  • Kamon J, Yamauchi T, Terauchi Y, Kubota N, Kadowaki T. The mechanisms by which PPARgamma and adiponectin regulate glucose and lipid metabolism]. Nihon Yakurigaku Zasshi. 2003;122:294–300.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Festuccia WT, Blanchard P-G & Deshaies Y. Control of brown adipose tissue glucose and lipid metabolism by PPARγ. Front Endocrinol. 2011;2:84.

  • Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, et al. PPARγ signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19:557–66.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Honda K, Marquillies P, Capron M, Dombrowicz D. Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model. J Allergy Clin Immunol. 2004;113:882–8.

    CAS 
    PubMed 

    Google Scholar
     

  • Benayoun L, Letuve S, Druilhe A, Boczkowski J, Dombret MC, Mechighel P, et al. Regulation of peroxisome proliferator-activated receptor gamma expression in human asthmatic airways: relationship with proliferation, apoptosis, and airway remodeling. Am J Respir Crit Care Med. 2001;164:1487–94.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nobs SP, Natali S, Pohlmeier L, Okreglicka K, Schneider C, Kurrer M, et al. PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation. J Exp Med. 2017;214:3015–35.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen T, Tibbitt CA, Feng X, Stark JM, Rohrbeck L, Rausch L, et al. PPAR-γ promotes type 2 immune responses in allergy and nematode infection. Sci Immunol. 2017;2:eaal5196.

  • Steiner CA, Janez A, Jensterle M, Reisinger K, Forst T, Pfützner A. Impact of treatment with rosiglitazone or metformin on biomarkers for insulin resistance and metabolic syndrome in patients with polycystic ovary syndrome. J Diab Sci Technol. 2007;1:211–7.

    Article 

    Google Scholar
     

  • Tfayli H, Ulnach JW, Lee S, Sutton-Tyrrell K, Arslanian S. Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors. J Clin Endocrinol Metab. 2011;96:1311–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wagstaff AJ, Goa KL. Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs. 2002;62:1805–37.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Deeks ED, Keam SJ. Rosiglitazone : a review of its use in type 2 diabetes mellitus. Drugs. 2007;67:2747–79.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Buettner R, Schölmerich J, Bollheimer LC. High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity. 2007;15:798–808.

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • de Moura EDM, Dos Reis SA, da Conceição LL, Sediyama C, Pereira SS, de Oliveira LL, et al. Diet-induced obesity in animal models: points to consider and influence on metabolic markers. Diabetol Metab Syndr. 2021;13:32.

    Article 

    Google Scholar