Defective immunosuppressive function of Treg cells in visceral adipose tissue in MIF deficient mice
2021
Document Type:
Article (Published version)
,
© 2020 Elsevier Ltd.
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Show full item recordAbstract:
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.
Keywords:
Obesity; Treg cells; MIF; IL-10; Visceral adipose tissue; Immunosuppressive functionSource:
Cytokine, 2021, 138, 155372-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.1016/j.cyto.2020.155372
ISSN: 1043-4666
PubMed: 33246771