Transglutaminase 2-expressing macrophages modulate adipose tissue inflammation

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dc.contributor.authorElizondo, Diana M.
dc.contributor.authorPatel, Tushar P.
dc.contributor.authorCole, Benjamin T.
dc.contributor.authorJansujwicz, Eliza A.
dc.contributor.authorChen, Jocelyn
dc.contributor.authorHollis, Melanie C.
dc.contributor.authorMitra, Apratim
dc.contributor.authorYanovski, Jack A.
dc.date.accessioned2025-07-09T17:55:46Z
dc.date.issued2025-06-04
dc.description.abstractWe investigated Transglutaminase 2 (TGM2) in high fat diet (HFD) obese mice, finding upregulated TGM2+ adipose tissue macrophages (ATMs) in HFD epididymal white adipose tissue (eWAT) compared to chow diet (CD) eWAT. Using Tgm2 CRISPR silencing, we examined TGM2 modulation of inflammation in vitro within bone marrow-derived macrophages (BMMs), as well as in co-cultured eWAT stromal vascular fraction (SVF) cells. Tgm2 silencing in BMMs led to increased pro-inflammation, compared to control. In contrast, in vitro exposure of eWAT SVF to recombinant TGM2 increased anti-inflammatory IL-10 secretion. However, IL-10 was not induced by recombinant TGM2 in CD activated CD4 + T cells, or in HFD-derived SVF CD4 + T cells. In vivo Tgm2 silencing in CD11b+ cells in HFD mice resulted in pro-inflammation in eWAT and serum, and increased adiposity and insulin resistance, suggesting that TGM2 + ATMs possess an anti-inflammatory role in obesity that is insufficient to reverse obesity-induced inflammation.
dc.description.sponsorshipThe authors thank Dr. K.O. for providing continuous feedback on this work, and the Flow Cytometry Core of the National Heart, Lung, and Blood Institute for flow cytometry data acquisition and the NICHD’s Bioinformatics and Scientific Programming Core. This work has been supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIAHD00641, to J.A.Y.) with supplemental funding from the Maximizing Opportunities for Scientific and Academic Independent Careers Postdoctoral Career Transition to Promote Diversity (1K99DK136921) and NICHD Early Career Investigator Awards (to D.M.E.).
dc.description.urihttps://www.nature.com/articles/s42003-025-08199-1
dc.format.extent14 pages
dc.genrejournal articles
dc.identifierdoi:10.13016/m2ypi3-9dk5
dc.identifier.citationDiana M. Elizondo et al., “Transglutaminase 2-Expressing Macrophages Modulate Adipose Tissue Inflammation,” Communications Biology 8, no. 1 (June 4, 2025): 1–14, https://doi.org/10.1038/s42003-025-08199-1.
dc.identifier.urihttps://doi.org/10.1038/s42003-025-08199-1
dc.identifier.urihttp://hdl.handle.net/11603/39344
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Faculty Collection
dc.relation.ispartofUMBC Biological Sciences Department
dc.rightsThis work was written as part of one of the author's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.
dc.rightsPublic Domain
dc.rights.urihttps://creativecommons.org/publicdomain/mark/1.0/
dc.subjectObesity
dc.subjectChronic inflammation
dc.titleTransglutaminase 2-expressing macrophages modulate adipose tissue inflammation
dc.typeText

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