C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation

Lee, Chang Hoon; Zhang, Hongwei H.; Singh, Satya P.; Koo, Lily Y.; Kabát, Juraj; Tsang, Hsinyi; Singh, Tejbir; Farber, Joshua M.

doi:10.7554/elife.32532

Cited by 26 publications

(29 citation statements)

References 100 publications

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“…As compared with single-positive conventional T cells, thymic MAIT cells expressed high levels of Ccr2 (Fig. 6 c; recently implicated in diapedesis to inflamed tissues; Lee et al, 2018), Ccr8 (potentially targeting to skin and lung tissues), and Cxcr6 (gut-liver tropism), as well as Ccr6 (skin, gut, and brain tropism) for MAIT17 cells and Cxcr3 (homing to inflamed tissues) for MAIT1 cells (Fig. 6 c).…”

Section: Resultsmentioning

confidence: 98%

“…Notably, in human blood, expression of the transcription factor Cebpd is almost specific of MAIT cells (Table S2 a). Cebpd expression has been associated with migration to tissues through inflamed endothelium in a CCR2-dependent process (Lee et al, 2018). However, in mice, Cebpd was not found expressed in any of our transcriptome datasets, nor in publicly available NKT gene expression datasets.…”

Section: Discussionmentioning

confidence: 99%

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A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets

Salou

Legoux

Gilet

et al. 2018

Journal of Experimental Medicine

145

151

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Mucosal-associated invariant T (MAIT) cells are abundant T cells with unique specificity for microbial metabolites. MAIT conservation along evolution indicates important functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed the first transcriptomic analysis of murine MAIT cells. MAIT1 (RORγtneg) and MAIT17 (RORγt+) subsets were markedly distinct from mainstream T cells, but quasi-identical to NKT1 and NKT17 subsets. The expression of similar programs was further supported by strong correlations of MAIT and NKT frequencies in various organs. In both mice and humans, MAIT subsets expressed gene signatures associated with tissue residency. Accordingly, parabiosis experiments demonstrated that MAIT and NKT cells are resident in the spleen, liver, and lungs, with LFA1/ICAM1 interactions controlling MAIT1 and NKT1 retention in spleen and liver. The transcriptional program associated with tissue residency was already expressed in thymus, as confirmed by adoptive transfer experiments. Altogether, shared thymic differentiation processes generate “preset” NKT and MAIT subsets with defined effector functions, associated with specific positioning into tissues.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets

Salou

Legoux

Gilet

et al. 2018

Journal of Experimental Medicine

145

151

View full text Add to dashboard Cite

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“…MAIT cells are present in the circulation and peripheral organs like liver, lungs, and the gastrointestinal mucosa. Indeed, MAIT cells efficiently leave the circulation and enter inflamed tissues without the need for phenotypic changes or activation in lymphoid organs [7]. When activated by cognate antigen recognition or by combinations of cytokines, MAIT cells rapidly secrete cytokines and up-regulate cytotoxicity-related molecules like Granzyme B (GrB) [8–10].…”

Section: Introductionmentioning

confidence: 99%

Tumor-infiltrating mucosal-associated invariant T (MAIT) cells retain expression of cytotoxic effector molecules

et al. 2019

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Mucosal-associated invariant T (MAIT) cells all express a semi-invariable T cell receptor recognizing microbial metabolites presented on the MHC class I-like molecule MR1. Upon activation, they rapidly secrete cytokines and increase their cytotoxic potential. We showed recently that MAIT cells with Th1 phenotype accumulate in human colon adenocarcinomas. Here, we investigated the cytotoxic potential of tumor-infiltrating MAIT cells in colon adenocarcinomas, and to what extent it may be affected by the tumor microenvironment. Activation of MAIT cells from tumors induced increased Granzyme B, and to a lesser extent, perforin expression. Degranulation was assessed by surface expression of CD107a, and was also seen in response to cognate antigen recognition. The cytotoxic potential of tumor-associated MAIT cells was very similar to that of MAIT cells from unaffected colon. MAIT cells were also identified by immunofluorescence in direct contact with tumor cells in sections from colon cancer specimens. To summarize, tumor-associated MAIT cells from colon tumors have strong cytotoxic potential and are not compromised in this regard compared to MAIT cells from the unaffected colon. We conclude that MAIT cells may contribute significantly to the protective immune response to tumors, both by secretion of Th1-associated cytokines and by direct killing of tumor cells.

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“…In our recent study 13 , we found that the C/EBP/δ-mediated transcriptional pathway in MAIT cells involves highly expressed inflammatory adhesion molecules, which include C-C chemokine receptor type 6 ( CCR6 ), fucosyltransferase 7 ( FUT7 ), and ST3 beta-galactoside alpha-2,3-sialyltransferase 4 ( ST3GAL4 ). The molecules participate in the synthesis of the sialic Lewis acid motif-glycosylation modification of selectin ligands.…”

Section: Introductionmentioning

confidence: 99%

Differences in the molecular signatures of mucosal-associated invariant T cells and conventional T cells

Park

Kim

et al. 2019

Sci Rep

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Mucosal-associated invariant T (MAIT) cells exhibit different characteristics from those of TCRα7.2 − conventional T cells. They play important roles in various inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease. MAIT cells express a single T cell receptor alpha chain, TCRα7.2 segment associated with Jα33 and CDR3 with fixed length, which recognizes bacteria-derived vitamin B metabolites. However, the characteristics of MAIT cells and TCRα7.2 + CD161 − T cells have never been compared. Here, we performed RNA sequencing to compare the properties of MAIT cells, TCRα7.2 − conventional T cells and TCRα7.2 + CD161 − T cells. Genome-wide transcriptomes of MAIT cells, TCRα7.2 − conventional T cells, and TCRα7.2 + CD161 − T cells were compared and analyzed using causal network analysis. This is the first report comparing the transcriptomes of MAIT cells, TCRα7.2 − conventional T cells and TCRα7.2 + CD161 − T cells. We also identified the predominant signaling pathways of MAIT cells, which differed from those of TCRα7.2 − conventional T cells and TCRα7.2 + CD161 − T cells, through a gene set enrichment test and upstream regulator analysis and identified the genes responsible for the characteristic MAIT cell phenotypes. Our study advances the complete understanding of MAIT biology.

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C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation

Cited by 26 publications

References 100 publications

A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets

A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets

Tumor-infiltrating mucosal-associated invariant T (MAIT) cells retain expression of cytotoxic effector molecules

Differences in the molecular signatures of mucosal-associated invariant T cells and conventional T cells

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