New Genetically Manipulated Mice Provide Insights Into the Development and Physiological Functions of Invariant Natural Killer T Cells.

Yue Ren,Thitinan Kasetthat,Hiroshi Watarai,Midori Tateyama,Etsuko Sekine-Kondo,Surasakadi Wongratanacheewin

doi:10.3389/fimmu.2018.01294

Abstract

Invariant natural killer T (iNKT) cells are a unique T cell subset that exhibits characteristics of both innate immune cells and T cells. They express Vα14-Jα18 (Trav11-Traj18) as an invariant chain of the T cell receptor (TCR) and are restricted to the MHC class I-like monomorphic antigen presenting molecule CD1d. iNKT cells are known as immune regulators that bridge the innate and acquired immune systems by rapid and massive production of a wide range of cytokines, which could enable them to participate in immune responses during various disease states. Thus, Traj18-deficient mice, Cd1d-deficient mice, or iNKT cell-overexpressing mice such as iNKT TCRα transgenic mice and iNKT cell cloned mice which contain a Vα14-Jα18 rearrangement in the TCRα locus are useful experimental models for the analysis of iNKT cells in vivo and in vitro. In this review, we describe the pros and cons of the various available genetically manipulated mice and summarize the insights gained from their study, including the possible roles of iNKT cells in obesity and diabetes.

Highlights

Invariant natural killer T cells are characterized by the expression of an invariant T cell receptor (TCR), Vα14-Jα18 (Trav11-Traj18) paired with Vβ8.2 (Trbv13-2), Vβ8.1 (Trbv13-3), Vβ7 (Trbv29), or Vβ2 (Trbv1) in mice and the Vα24-Jα18/Vβ11Dβ2-Jβ2.7 (TRAV10-TRAJ18/TRBV25-1-TRBD2-TRBJ2-7) pair in humans
When activated by α-GalCer, Invariant natural killer T (iNKT) cells rapidly produce these various types of cytokines, resulting in bystander immune modulating functions leading to activation and inhibition of various immune effector cells, including NK cells, macrophages, granulocytes, dendritic cells (DCs), basophils, and eosinophils in the innate system as well as CD4+ T and CD8+ T cells in the acquired system
If we focus only on the results obtained from B6 background Traj18−/− mice, it is interesting to note that most of the studies have used an high fat diet (HFD) of 60% fat calories, and none of them have reported a decreased level of weight gain in Traj18−/− mice as compared with WT B6 mice [36,37,38,39,40]

Summary

INTRODUCTION

Invariant natural killer T (iNKT) cells ( called type I NKT cells) are characterized by the expression of an invariant T cell receptor (TCR), Vα14-Jα18 (Trav11-Traj18) paired with Vβ8.2 (Trbv13-2), Vβ8.1 (Trbv13-3), Vβ7 (Trbv29), or Vβ2 (Trbv1) in mice and the Vα24-Jα18/Vβ11Dβ2-Jβ2.7 (TRAV10-TRAJ18/TRBV25-1-TRBD2-TRBJ2-7) pair in humans. Kotas et al [40] and Lee et al [41] have reported a minor role of iNKT cells in the development of obesity, by comparing Traj18−/− and Cd1d1−/−C d1d2−/− mice with WT B6 mice on an HFD Many reasons for these divergent results have been proposed and discussed, including the age, gender, and background of the mice, HFD type and duration, and the gut flora or environmental microbial distribution among the animals employed by the different research groups. The frequency of positive cells of CD44, CD4, and NK1.1 by thymic α-GalCer/ CD1d dimer+TCRβ+ cells from Cd1d1−/−Trav11-Traj18+/+ mice is further lower than those from Trav11-Traj18+/+ mice (Figure 2A), suggesting that CD1d plays a role in the induction of these surface molecules on iNKT cells

IN THE THYMUS

Findings

CONCLUSION