Defective immunosuppressive function of Treg cells in visceral adipose tissue in MIF deficient mice. (February 2021)

• Record Type: Journal Article
• Authors: Gajic, Dragica; Koprivica, Ivan; Stojanovic, Ivana; Saksida, Tamara
• Is Part Of: Cytokine. Volume 138(2021)
• Publication Date: 2021-02
• Subjects: Obesity -- Treg cells -- MIF -- IL-10 -- Visceral adipose tissue -- Immunosuppressive function; AT Adipose tissue -- VAT Visceral adipose tissue -- SVF Stromal vascular fraction -- MIF Macrophage migration inhibitory factor -- IR Insulin resistance -- Treg Regulatory T lymphocytes -- PPARγ Peroxisome proliferator-activated receptor γ -- HFD High fat diet -- WT Wild type -- PBS Phosphate-buffered saline -- BrdU 5-bromo-2′-deoxyuridine -- ATCM Adipose tissue conditioned media; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155372
• Languages: English
• ISSNs: 1043-4666

Abstract

Graphical abstract: Highlights: MIF deletion promotes obesity and VAT inflammation. Treg cells are numerous in MIF −/− VAT. Insufficient IL-10 and TGF-β expression/secretion in MIF −/− VAT. Significantly lower levels of STAT3 and IL-33 in MIF −/− VAT. MIF is necessary for immunosuppressive Treg action in VAT. Abstract: Obesity, a global health problem nowadays, is a state of low-grade chronic inflammation of adipose tissue (AT) associated with increased adipocyte growth and proliferation and immune cell polarization towards an inflammatory phenotype within the stromal vascular fraction (SVF). Pro-inflammatory cells in the AT produce mediators of inflammation (IL-1β, TNF, macrophage migration inhibitory factor – MIF), thereby surpassing the anti-inflammatory response mediated by IL-10 and TGF-β, cytokines produced by regulatory T (Treg) cells. In this study we demonstrate that the absence of the pro-inflammatory cytokine MIF led to obesity and inflammation in the visceral AT (VAT) in 6 months old MIF −/− mice. Besides the increment of pro-inflammatory AT macrophages and the enhanced production of TNF and IL-1β, VAT of MIF −/− mice contained increased numbers of Treg cells. In situ proliferation of Treg cells did not differ between MIF −/− and wild type mice, but Treg cells isolated from the VAT of MIF-deficient mice, and not from the cervical lymph nodes, exhibited lower expression and production of IL-10 and TGF-β. Additionally, SVF cells had significantly lower levels of STAT3 and IL-33, altogether indicating that VAT Treg cells in MIF −/− mice, albeit abundantly present, are not fully functional. These results indicate that MIF is a new regulator of VAT Treg cell function, necessary for their immunosuppressive activities.