Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq.

Ying Yao,Shuo-Wang Qiao,Łukasz Wyrozżemski,Knut E A Lundin,Geir Kjetil Sandve

doi:10.1371/journal.pone.0258029

Abstract

Gluten-specific CD4+ T cells drive the pathogenesis of celiac disease and circulating gluten-specific T cells can be identified by staining with HLA-DQ:gluten tetramers. In this first single-cell RNA-seq study of tetramer-sorted T cells from untreated celiac disease patients blood, we found that gluten-specific T cells showed distinct transcriptomic profiles consistent with activated effector memory T cells that shared features with Th1 and follicular helper T cells. Compared to non-specific cells, gluten-specific T cells showed differential expression of several genes involved in T-cell receptor signaling, translational processes, apoptosis, fatty acid transport, and redox potentials. Many of the gluten-specific T cells studied shared T-cell receptor with each other, indicating that circulating gluten-specific T cells belong to a limited number of clones. Moreover, the transcriptional profiles of cells that shared the same clonal origin were transcriptionally more similar compared with between clonally unrelated gluten-specific cells.

Highlights

Celiac disease (CD) is an autoimmune disorder that primarily affects the small intestine
Effector memory (CD62L-CD45RA-) CD4+ T cells were sorted as either gluten-specific T cells that bound to human leukocyte antigen (HLA)-DQ2.5:gluten tetramers presenting one of the four immunodominant gluten epitopes, hereafter denoted as tetramer-positive cells, or effector memory T cells that were tetramer-negative (S1 Fig)
Gluten-specific CD4+ T cells are the key drivers for the pathogenesis of celiac disease

Summary

Introduction

Celiac disease (CD) is an autoimmune disorder that primarily affects the small intestine. It is caused by an adverse reaction to gluten, which is a group of proteins typically found in wheat, rye and barley. The vast majority of celiac disease patients express human leukocyte antigen (HLA)-DQ2.5 (HLA-DQA1 05/HLA-DQB1 02, expressed by 90% of patients), and the remaining patients are either HLA-DQ8 (HLA-DQA1 03/ HLA-DQB1 03:02) or HLA- DQ2.2 (HLA-DQA1 02:01/HLA-DQB1 02) [2, 3]. The strong major histocompatibility complex (MHC) class II association shows that CD4+ T cells play an important role in the pathogenesis of celiac disease.

Methods

Results

Conclusion