The importance of T cells of the innate immune system in the development of meta-inflammation of adipose tissue in obesity


  • A.E. Abaturov State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine”, Dnipro, Ukraine
  • A.А. Nikulina State Institution “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine”, Dnipro, Ukraine



obesity, meta-inflammation, innate immune system, T cells, review


This review of the scientific literature deals with the participation of αβT and γδT cells of the innate immune system in maintaining an anti-inflammatory environment in the physiological state of adipose tissue and their role in the development of meta-inflammation in obesity. Overweight due to an increase in adipose tissue is associated with the development of metabolic disorders, which not only significantly reduce the quality of life, but also have the risk of adverse cardiovascular events. According to modern concepts, the trigger of metabolic disorders is low-grade inflammation induced by adipocyte dysfunction in obesity. Metabolically active cells such as adipocytes in obesity secrete numerous anti-inflammatory cytokines and chemokines, which recruit various immune cells into adipose tissue or activate cells of the immune system, including T cells of the innate immune system. In obesity, mucosal-associated invariant T (MAIT) cells of adipose tissue express an overactivated phenotype and are characterized by unresponsiveness to signals of the TCR-associated pathway, significantly increasing in obese children than in children with physiological body weight. The data are presented on the importance of invariant natural killer T (iNKT) cells, which critically administer the functioning of Treg cells and macrophages in adipose tissue, activation of which causes not only the death of adipocytes, but also stimulates adipogenesis that promotes insulin-dependent glucose uptake by adipocytes, and, in turn, a decrease in the number of iNKT cells, which observed in obesity, leads to the development of meta-inflammation. Variable NKT cells excite plasmacytoid dendritic cells and induce a tolerogenic effect on conventional dendritic cells. The data are given that a decrease in the representation of γδT cells in adipose tissue in obesity determines the intensity of meta-inflammation and insulin resistance in experimental animals receiving a high-fat diet. In the near future, drug control of the activity of MAIT, NKT, and γδT cells may become one of the possible ways to suppress the activity of obesity-induced meta-inflammation and prevent the development of metabolic disorders.


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Abaturov AE. Metabolic syndrome in children (lecture). Tavricheskiy Mediko-Biologicheskiy Vestnik. 2007;10:57-65. (in Russian).

Abaturov AE. Features of metabolic syndrome in children. Dytiachyi likar. 2011; 4 (11): 54 -61. (in Russian).

Bokova TA. Non-alcoholic fatty hepatic disease in children with obesity and metabolic syndrome. Lechaschi Vrach. 2019;(1):28-31. (in Russian).

Veitsman IA, Kuzmina AD, Andrienko AV, Belov MA. Obesity: promising pathogenetic directions for the treatment of obesity (literature review). Modern Science: actual problems of theory and practice", a series "Natural and Technical Sciences. 2020;1:168-171. (in Russian).

Agrawal M, Kern PA, Nikolajczyk BS. The Immune System in Obesity: Developing Paradigms Amidst Inconvenient Truths. Curr Diab Rep. 2017 Aug 15;17(10):87. doi: 10.1007/s11892-017-0917-9.

Attaf M, Legut M, Cole DK, Sewell AK. The T cell antigen receptor: the Swiss army knife of the immune system. Clin Exp Immunol. 2015 Jul;181(1):1-18. doi: 10.1111/cei.12622.

Bertrand L, Lehuen A. MAIT cells in metabolic diseases. Mol Metab. 2019 Sep;27S(Suppl):S114-S121. doi: 10.1016/j.molmet.2019.06.025.

Born WK, Kemal Aydintug M, O'Brien RL. Diversity of γδ T-cell antigens. Cell Mol Immunol. 2013 Jan;10(1):13-20. doi: 10.1038/cmi.2012.45.

Brennan PJ, Brigl M, Brenner MB. Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol. 2013 Feb;13(2):101-17. doi: 10.1038/nri3369.

Carolan E, Tobin LM, Mangan BA, et al. Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity. J Immunol. 2015;194(12):5775-5780. doi:10.4049/jimmunol.1402945.

Chandra S, Kronenberg M. Activation and Function of iNKT and MAIT Cells. Adv Immunol. 2015;127:145-201. doi: 10.1016/

Choe SS, Huh JY, Hwang IJ, Kim JI, Kim JB. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders. Front Endocrinol (Lausanne). 2016 Apr 13;7:30. doi: 10.3389/fendo.2016.00030.

Contreras AV, Wiest DL. Recent advances in understanding the development and function of γδ T cells. F1000Res. 2020 Apr 29;9:F1000 Faculty Rev-306. doi: 10.12688/f1000research.22161.1.

Costanzo AE, Taylor KR, Dutt S, Han PP, Fujioka K, Jameson JM. Obesity impairs γδ T cell homeostasis and antiviral function in humans. PLoS One. 2015 Mar 18;10(3):e0120918. doi: 10.1371/journal.pone.0120918.

Crosby CM, Kronenberg M. Invariant natural killer T cells: front line fighters in the war against pathogenic microbes. Immunogenetics. 2016 Aug;68(8):639-48. doi: 10.1007/s00251-016-0933-y.

Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010 Jul;10(7):479-89. doi: 10.1038/nri2800.

Dasgupta S, Kumar V. Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset. Immunogenetics. 2016 Aug;68(8):665-76. doi: 10.1007/s00251-016-0930-1.

Davey MS, Willcox CR, Baker AT, Hunter S, Willcox BE. Recasting Human Vδ1 Lymphocytes in an Adaptive Role. Trends Immunol. 2018 Jun;39(6):446-459. doi: 10.1016/

Del Cornò M, D'Archivio M, Conti L, et al. Visceral fat adipocytes from obese and colorectal cancer subjects exhibit distinct secretory and ω6 polyunsaturated fatty acid profiles and deliver immunosuppressive signals to innate immunity cells. Oncotarget. 2016 Sep 27;7(39):63093-63105. doi: 10.18632/oncotarget.10998.

Dhodapkar MV, Kumar V. Type II NKT Cells and Their Emerging Role in Health and Disease. J Immunol. 2017 Feb 1;198(3):1015-1021. doi: 10.4049/jimmunol.1601399.

Fay NS, Larson EC, Jameson JM. Chronic Inflammation and γδ T Cells. Front Immunol. 2016 May 27;7:210. doi: 10.3389/fimmu.2016.00210.

Franciszkiewicz K, Salou M, Legoux F, Zhou Q, Cui Y, Bessoles S, Lantz O. MHC class I-related molecule, MR1, and mucosal-associated invariant T cells. Immunol Rev. 2016 Jul;272(1):120-38. doi: 10.1111/imr.12423.

Garner LC, Klenerman P, Provine NM. Insights Into Mucosal-Associated Invariant T Cell Biology From Studies of Invariant Natural Killer T Cells. Front Immunol. 2018 Jun 28;9:1478. doi: 10.3389/fimmu.2018.01478.

Gibbons D, Fleming P, Virasami A, et al. Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants. Nat Med. 2014 Oct;20(10):1206-10. doi: 10.1038/nm.3670.

Godfrey DI, Koay HF, McCluskey J, Gherardin NA. The biology and functional importance of MAIT cells. Nat Immunol. 2019 Sep;20(9):1110-1128. doi: 10.1038/s41590-019-0444-8.

Hams E, Locksley RM, McKenzie AN, Fallon PG. Cutting edge: IL-25 elicits innate lymphoid type 2 and type II NKT cells that regulate obesity in mice. J Immunol. 2013 Dec 1;191(11):5349-53. doi: 10.4049/jimmunol.1301176.

Huh JY, Park J, Kim JI, Park YJ, Lee YK, Kim JB. Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity. Diabetes. 2017 Apr;66(4):835-847. doi: 10.2337/db16-1122.

Huh JY, Park YJ, Kim JB. Adipocyte CD1d determines adipose inflammation and insulin resistance in obesity. Adipocyte. 2018;7(2):129-136. doi: 10.1080/21623945.2018.1440928.

Ivanov S, Paget C, Trottein F. Role of non-conventional T lymphocytes in respiratory infections: the case of the pneumococcus. PLoS Pathog. 2014 Oct 9;10(10):e1004300. doi: 10.1371/journal.ppat.1004300.

Johnson MD, Witherden DA, Havran WL. The Role of Tissue-resident T Cells in Stress Surveillance and Tissue Maintenance. Cells. 2020 Mar 11;9(3):686. doi: 10.3390/cells9030686.

Keller AN, Corbett AJ, Wubben JM, McCluskey J, Rossjohn J. MAIT cells and MR1-antigen recognition. Curr Opin Immunol. 2017 Jun;46:66-74. doi: 10.1016/j.coi.2017.04.002.

Kohlgruber AC, Donado CA, LaMarche NM, Brenner MB, Brennan PJ. Activation strategies for invariant natural killer T cells. Immunogenetics. 2016 Aug;68(8):649-63. doi: 10.1007/s00251-016-0944-8.

Kohlgruber AC, Gal-Oz ST, LaMarche NM, et al. γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis. Nat Immunol. 2018 May;19(5):464-474. doi: 10.1038/s41590-018-0094-2.

LaMarche NM, Kohlgruber AC, Brenner MB. Innate T Cells Govern Adipose Tissue Biology. J Immunol. 2018 Oct 1;201(7):1827-1834. doi: 10.4049/jimmunol.1800556.

Le Menn G, Sibille B, Murdaca J, et al. Decrease in αβ/γδ T-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin resistance, and inflammation. FASEB J. 2019 Feb;33(2):2553-2562. doi: 10.1096/fj.201800696RR.

Lee HW, Chung YS, Kim TJ. Heterogeneity of Human γδ T Cells and Their Role in Cancer Immunity. Immune Netw. 2020 Feb 14;20(1):e5. doi: 10.4110/in.2020.20.e5.

Li Y, Woods K, Parry-Strong A, et al. Distinct Dysfunctional States of Circulating Innate-Like T Cells in Metabolic Disease. Front Immunol. 2020 Mar 13;11:448. doi: 10.3389/fimmu.2020.00448.

Liu R, Nikolajczyk BS. Tissue Immune Cells Fuel Obesity-Associated Inflammation in Adipose Tissue and Beyond. Front Immunol. 2019 Jul 17;10:1587. doi: 10.3389/fimmu.2019.01587.

Luck H, Tsai S, Chung J, al. Regulation of obesity-related insulin resistance with gut anti-inflammatory agents. Cell Metab. 2015 Apr 7;21(4):527-42. doi: 10.1016/j.cmet.2015.03.001.

Lynch L, Hogan AE, Duquette D, et al. iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy. Cell Metab. 2016;24(3):510-519. doi:10.1016/j.cmet.2016.08.003.

Lynch L, Michelet X, Zhang S, et al. Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue. Nat Immunol. 2015;16(1):85-95. doi:10.1038/ni.3047.

Lynch L, Nowak M, Varghese B, et al. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity. 2012;37(3):574-587. doi:10.1016/j.immuni.2012.06.016.

Mamedov MR, Scholzen A, Nair RV, et al. A Macrophage Colony-Stimulating-Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence. Immunity. 2018;48(2):350-363.e7. doi:10.1016/j.immuni.2018.01.009.

Mathews JA, Williams AS, Brand JD, et al. γδ T cells are required for pulmonary IL-17A expression after ozone exposure in mice: role of TNFα. PLoS One. 2014;9(5):e97707. Published 2014 May 13. doi:10.1371/journal.pone.0097707.

Monteiro-Sepulveda M, Touch S, Mendes-Sá C, et al. Jejunal T cell inflammation in human obesity correlates with decreased enterocyte insulin signaling. Cell Metab. 2015;22(1):113–24. doi:10.1016/j.cmet.2015.05.020.

Morita CT, Mariuzza RA, Brenner MB. Antigen recognition by human gamma delta T cells: pattern recognition by the adaptive immune system. Springer Semin Immunopathol. 2000;22(3):191-217. doi: 10.1007/s002810000042.

O'Brien A, Loftus RM, Pisarska MM, et al. Obesity Reduces mTORC1 Activity in Mucosal-Associated Invariant T Cells, Driving Defective Metabolic and Functional Responses. J Immunol. 2019;202(12):3404-3411. doi:10.4049/jimmunol.1801600.

Park J, Huh JY, Oh J, et al. Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity. Genes Dev. 2019;33(23-24):1657-1672. doi:10.1101/gad.329557.119.

Parkinson RM, Collins SL, Horton MR, Powell JD. Egr3 induces a Th17 response by promoting the development of γδ T cells. PLoS One. 2014 Jan 24;9(1):e87265. doi: 10.1371/journal.pone.0087265.

Paul S, Singh AK, Shilpi, Lal G. Phenotypic and functional plasticity of gamma-delta (γδ) T cells in inflammation and tolerance. Int Rev Immunol. 2014 Nov-Dec;33(6):537-58. doi: 10.3109/08830185.2013.863306.

Peters C, Kabelitz D, Wesch D. Regulatory functions of γδ T cells. Cell Mol Life Sci. 2018 Jun;75(12):2125-2135. doi: 10.1007/s00018-018-2788-x.

Pisarska MM, Dunne MR, O'Shea D, Hogan AE. Interleukin-17 producing mucosal associated invariant T cells - emerging players in chronic inflammatory diseases? Eur J Immunol. 2020 Jul 3. doi: 10.1002/eji.202048645. Epub ahead of print.

Qin G, Liu Y, Zheng J, et al. Type 1 responses of human Vγ9Vδ2 T cells to influenza A viruses. J Virol. 2011;85(19):10109-10116. doi:10.1128/JVI.05341-11.

Rahimpour A, Koay HF, Enders A, et al. Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers. J Exp Med. 2015;212(7):1095-1108. doi:10.1084/jem.20142110.

Rampoldi F, Ullrich L, Prinz I. Revisiting the Interaction of γδ T-Cells and B-Cells. Cells. 2020;9(3):743. doi:10.3390/cells9030743.

Salio M, Silk JD, Jones EY, Cerundolo V. Biology of CD1- and MR1-restricted T cells. Annu Rev Immunol. 2014;32:323-66. doi: 10.1146/annurev-immunol-032713-120243.

Satoh M, Andoh Y, Clingan CS, et al. Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance. PLoS One. 2012;7(2):e30568. doi:10.1371/journal.pone.0030568.

Satoh M, Iwabuchi K. Role of Natural Killer T Cells in the Development of Obesity and Insulin Resistance: Insights From Recent Progress. Front Immunol. 2018;9:1314. doi:10.3389/fimmu.2018.01314.

Shiromizu CM, Jancic CC. γδ T Lymphocytes: An Effector Cell in Autoimmunity and Infection. Front Immunol. 2018;9:2389. Published 2018 Oct 16. doi:10.3389/fimmu.2018.02389.

Silva-Santos B, Serre K, Norell H. γδ T cells in cancer. Nat Rev Immunol. 2015;15(11):683-691. doi:10.1038/nri3904.

Singh AK, Rhost S, Löfbom L, Cardell SL. Defining a novel subset of CD1d-dependent type II natural killer T cells using natural killer cell-associated markers. Scand J Immunol. 2019;90(3):e12794. doi:10.1111/sji.12794.

Singh AK, Tripathi P, Cardell SL. Type II NKT Cells: An Elusive Population With Immunoregulatory Properties. Front Immunol. 2018;9:1969. Published 2018 Aug 28. doi:10.3389/fimmu.2018.01969.

Subramanian S, Goodspeed L, Wang S, et al. Deficiency of Invariant Natural Killer T Cells Does Not Protect Against Obesity but Exacerbates Atherosclerosis in Ldlr-/- Mice. Int J Mol Sci. 2018;19(2):510. doi:10.3390/ijms19020510.

Tatituri RV, Watts GF, Bhowruth V, et al. Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs. Proc Natl Acad Sci U S A. 2013;110(5):1827-1832. doi:10.1073/pnas.1220601110.

Taylor KR, Mills RE, Costanzo AE, Jameson JM. Gammadelta T cells are reduced and rendered unresponsive by hyperglycemia and chronic TNFalpha in mouse models of obesity and metabolic disease. PLoS One. 2010;5(7):e11422. Published 2010 Jul 2. doi:10.1371/journal.pone.0011422.

Tezze C, Romanello V, Sandri M. FGF21 as Modulator of Metabolism in Health and Disease. Front Physiol. 2019;10:419. Published 2019 Apr 17. doi:10.3389/fphys.2019.00419.

Toubal A, Nel I, Lotersztajn S, Lehuen A. Mucosal-associated invariant T cells and disease. Nat Rev Immunol. 2019;19(10):643-657. doi:10.1038/s41577-019-0191-y.

Touch S, Assmann KE, Aron-Wisnewsky J, et al; MetaCardis Consortium. Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders. FASEB J. 2018 Apr 27:fj201800052RR. doi: 10.1096/fj.201800052RR.

Touch S, Clément K, André S. T Cell Populations and Functions Are Altered in Human Obesity and Type 2 Diabetes. Curr Diab Rep. 2017;17(9):81. doi:10.1007/s11892-017-0900-5.

Tyler CJ, Doherty DG, Moser B, Eberl M. Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system. Cell Immunol. 2015;296(1):10-21. doi:10.1016/j.cellimm.2015.01.008.

Uhlen M, Karlsson MJ, Zhong W, et al. A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science. 2019;366(6472):eaax9198. doi:10.1126/science.aax9198.

van Eijkeren RJ, Krabbe O, Boes M, Schipper HS, Kalkhoven E. Endogenous lipid antigens for invariant natural killer T cells hold the reins in adipose tissue homeostasis. Immunology. 2018;153(2):179-189. doi:10.1111/imm.12839.

Wang Y, Sedimbi S, Löfbom L, Singh AK, Porcelli SA, Cardell SL. Unique invariant natural killer T cells promote intestinal polyps by suppressing TH1 immunity and promoting regulatory T cells. Mucosal Immunol. 2018;11(1):131-143. doi:10.1038/mi.2017.34.

Wensveen FM, Valentić S, Šestan M, Turk Wensveen T, Polić B. The "Big Bang" in obese fat: Events initiating obesity-induced adipose tissue inflammation. Eur J Immunol. 2015;45(9):2446-2456. doi:10.1002/eji.201545502.

Xu W, Lau ZWX, Fulop T, Larbi A. The Aging of γδ T Cells. Cells. 2020 May 9;9(5):1181. doi: 10.3390/cells9051181.

Zhang H, Xue R, Zhu S, et al. M2-specific reduction of CD1d switches NKT cell-mediated immune responses and triggers metaflammation in adipose tissue. Cell Mol Immunol. 2018;15(5):506-517. doi:10.1038/cmi.2017.11.



How to Cite

Abaturov, A., & Nikulina, A. (2021). The importance of T cells of the innate immune system in the development of meta-inflammation of adipose tissue in obesity. CHILD`S HEALTH, 15(8), 546–558.



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