bims-maitce 2023-12-17 papers

Issue of 2023‒12‒17
two papers selected by
Andy E. Hogan, Maynooth University

Nan Fang Yi Ke Da Xue Xue Bao. 2023 Nov 20. 43(11): 1881-1885

[Cold stimulation promotes interleukin-4 secretion by mucosal-associated invariant T cells in the adipose tissue to promote adipose browning in mice].

X Ye, Y Song, Y Zhao, D Zhu.

OBJECTIVE: To investigate the role of mucosal-associated invariant T (MAIT) cells in the regulatory mechanism of adipose browning.METHODS: A mouse model with functional deficiency of MAIT cells was established for comparison with the wild-type mice for levels of brown adipose tissue markers in response to cold stimulation using Western blotting and RT-PCR. Flow cytometry was used to analyze the changes in the number, activation level and cytokine secretion ability of MAIT cells in mouse adipose tissue after cold stimulation. In a co-culture system of MAIT cells and adipocytes, the effect of interleukin-4 (IL-4) blocking antibodies on the expressions of brown adipose tissue markers in the adipocytes was evaluated using Western blotting and RT-PCR. In a mouse model of MAIT cell deficiency, the changes in adipose browning-related indicators in response to cold stimulation were analyzed using metabolic cages, immunohistochemistry, Western blotting and the Seahorse method.
RESULTS: In both the mouse models of functional deficiency of MAIT cells and wild-type mice, cold stimulation significantly increased the expression levels of brown adipose tissue markers UCP-1 and PGC1-α and upregulated CD69 and IL-4 expressions in the adipose tissue without significantly affecting the number of MAIT cells in the adipose tissue. In the coculture experiment, the adipocytes showed obviously increased browning level after co-culture with MAIT cells (P < 0.05), but blocking IL-4 signaling strongly downregulated the browning level (P < 0.05). The MAIT cell-deficient mice showed obviously lower levels of energy expenditure, adipose browning and metabolism of the adipocytes compared with the wild-type mice in response to cold stimulation (P < 0.05).
CONCLUSION: MAIT cells participate in adipose browning in mice, and cold stimulation promotes MAIT cell secretion of IL-4 to positively regulate adipose browning.

Keywords: brown adipose tissue; mucosal-associated invariant T cells; obesity

DOI: https://doi.org/10.12122/j.issn.1673-4254.2023.11.07

bioRxiv. 2023 Dec 01. pii: 2023.11.29.569225. [Epub ahead of print]

MAIT cells drive chronic inflammation in a genetically diverse murine model of spontaneous colitis.

Liyen Loh, David Orlicky, Andrea Spengler, Cassandra Levens, Sofia Celli, Joanne Domenico, Jared Klarquist, Joseph Onyiah, Jennifer Matsuda, Kristine Kuhn, Laurent Gapin.

Background & aims: Lymphocytes that produce IL-17 can confer protective immunity during infections by pathogens, yet their involvement in inflammatory diseases is a subject of debate. Although these cells may perpetuate inflammation, resulting in tissue damage, they are also capable of contributing directly or indirectly to tissue repair, thus necessitating more detailed investigation. Mucosal-Associated-Invariant-T (MAIT) cells are innate-like T cells, acquiring a type III phenotype in the thymus. Here, we dissected the role of MAIT cells in vivo using a spontaneous colitis model in a genetically diverse mouse strain.Methods: Multiparameter spectral flow cytometry and scRNAseq were used to characterize MAIT and immune cell dynamics and transcriptomic signatures respectively, in the collaborative-cross strain, CC011/Unc and CC011/Unc- Traj33 -/- .
Results: In contrast to many conventional mouse laboratory strains, the CC011 strain harbors a high baseline population of MAIT cells. We observed an age-related increase in colonic MAIT cells, Th17 cells, regulatory T cells, and neutrophils, which paralleled the development of spontaneous colitis. This progression manifested histological traits reminiscent of human IBD. The transcriptomic analysis of colonic MAIT cells from CC011 revealed an activation profile consistent with an inflammatory milieu, marked by an enhanced type-III response. Notably, IL-17A was abundantly secreted by MAIT cells in the colons of afflicted mice. Conversely, in the MAIT cell-deficient CC011-Traj33-/- mice, there was a notable absence of significant colonic histopathology. Furthermore, myeloperoxidase staining indicated a substantial decrease in colonic neutrophils.
Conclusions: Our findings suggest that MAIT cells play a pivotal role in modulating the severity of intestinal pathology, potentially orchestrating the inflammatory process by driving the accumulation of neutrophils within the colonic environment.

DOI: https://doi.org/10.1101/2023.11.29.569225