Role of CD1d- and MR1-Restricted T Cells in Asthma.

Chiaki Iwamura,Toshinori Nakayama

doi:10.3389/fimmu.2018.01942

Abstract

Innate T lymphocytes are a group of relatively recently identified T cells that are not involved in either innate or adaptive immunity. Unlike conventional T cells, most innate T lymphocytes express invariant T cell receptor to recognize exogenous non-peptide antigens presented by a family of non-polymorphic MHC class I-related molecules, such as CD1d and MHC-related molecule-1 (MR1). Invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells quickly respond to the antigens bound to CD1d and MR1 molecules, respectively, and immediately exert effector functions by secreting various cytokines and granules. This review describes the detrimental and beneficial roles of iNKT cells in animal models of asthma and in human asthmatic patients and also addresses the mechanisms through which iNKT cells are activated by environmental or extracellular factors. We also discuss the potential for therapeutic interventions of asthma by specific antibodies against NKT cells. Furthermore, we summarize the recent reports on the role of MAIT cells in allergic diseases.

Highlights

Innate-like T cells (CD1-restricted T cells or MHC-related molecule-1 (MR1)-restricted T cells) are classified as innate lymphoid cells that have features similar to those of the cells involved in acquired immunity, such as T cell receptor (TCR) expression [1]
Our previous study showed that α-GalCer induced airway hyperactivity (AHR) and neutrophilic infiltration, and the neutrophilic infiltration was significantly attenuated in CD69deficient mice, indicating that activated invariant natural killer T (iNKT) cells-mediated asthmatic responses were dependent on CD69 expression [5]
IL-33 enhanced the production of Th1 and Th2 cytokines in activated NKT cells [68, 69]. These results indicate that natural ligands in the environments act as antigens for iNKT cells to induce allergic asthma, and TCR-independent stimuli to iNKT cells may exacerbate the asthmatic symptoms such as AHR (Figure 1)

Summary

Introduction

Innate-like T cells (CD1-restricted T cells or MHC-related molecule-1 (MR1)-restricted T cells) are classified as innate lymphoid cells that have features similar to those of the cells involved in acquired immunity, such as T cell receptor (TCR) expression [1]. The administration of α-GalCer or glycolipid derived from Helicobacter pylori to neonates recapitulated the result [41], suggesting that infection with certain microorganisms can prevent the subsequent development of allergic asthma by expanding a specific subset of iNKT cells. Our previous study showed that α-GalCer induced AHR and neutrophilic infiltration, and the neutrophilic infiltration was significantly attenuated in CD69deficient mice, indicating that activated iNKT cells-mediated asthmatic responses were dependent on CD69 expression [5].

Results

Conclusion