Abstract

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.

Highlights

  • TCRα7.2 segment associated with Jα33 and CDR3 with fixed length, which recognizes bacteria-derived vitamin B metabolites

  • We identified previously unreported genes (SLCA4A10, SCART1, WNT11, LTK, FLT4, LEF1, KLRC4, TBC1D4, LAIR2, KLRB1, ZFP36L2, DUSP2, ARL4C, SNORA70, LDHB, ITK, FYB, MIAT, and TMEM173, among others) that may determine the characteristics of mucosal-associated invariant T (MAIT) cells

  • The results reveal a marked difference between TCRα7.2+ CD161− T cells and MAIT cells, with the former being nearly identical to conventional T cells

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Summary

Introduction

TCRα7.2 segment associated with Jα33 and CDR3 with fixed length, which recognizes bacteria-derived vitamin B metabolites. MAIT cells recognize bacterial-derived vitamin B metabolites restricted by the MHC class I-like protein MR12–5 These antigens are beyond the boundaries of those recognized by conventional T cells, which have highly diverse TCR molecules restricted by MHC class I or MHC class II. Other recent studies have revealed the critical role of MAIT cells in various inflammatory diseases, including ulcerative colitis, psoriasis and several cancers This is in addition to their role in defeating bacterial pathogens[9,10,11,12]. We performed genome-scale analysis of gene expression profiles using RNA sequencing (RNA-Seq) based on next-generation sequencing methods This was done to better understand the potential causative molecular characteristics of the unique cellular effector functions of MAIT cells, which differ from conventional T cells.

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