How Mucosal Epithelia Deal with Stress: Role of NKG2D/NKG2D Ligands during Inflammation.

Fabrizio Antonangeli,Cristina Cerboni,Giuseppe Sciumè,Alessandra Soriani,Angela Santoni

doi:10.3389/fimmu.2017.01583

Abstract

Mucosal epithelia encounter both physicochemical and biological stress during their life and have evolved several mechanisms to deal with them, including regulation of immune cell functions. Stressed and damaged cells need to be cleared to control local inflammation and trigger tissue healing. Engagement of the activating NKG2D receptor is one of the most direct mechanisms involved in the recognition of stressed cells by the immune system. Indeed, injured cells promptly express NKG2D ligands that in turn mediate the activation of lymphocytes of both innate and adaptive arms of the immune system. This review focuses on different conditions that are able to modulate NKG2D ligand expression on the epithelia. Special attention is given to the mechanisms of immunosurveillance mediated by natural killer cells, which are finely tuned by NKG2D. Different types of stress, including viral and bacterial infections, chronic inflammation, and cigarette smoke exposure, are discussed as paradigmatic conditions for NKG2D ligand modulation, and the implications for tissue homeostasis are discussed.

Highlights

Mucosal epithelia represent the frontline of multicellular organisms, and they are continuously exposed to several types of stress
This review focuses on different conditions that are able to modulate NKG2D ligands on epithelial cells, and, in particular, on the role of NKG2D/NKG2D ligands in controlling the homeostasis of the gut and lung epithelia during inflammation
NKG2D ligands may have a wider role than stress sensors, contributing to the homeostatic control of the immune system, since a study by La Scaleia and colleagues has shown that NKG2D ligands, namely MICA/B and ULBP1–2, are upregulated on the epithelium of gut and on the immune infiltrate in inflammatory bowel disease (IBD) lesions [38]

Summary

INTRODUCTION

Mucosal epithelia represent the frontline of multicellular organisms, and they are continuously exposed to several types of stress. Upon stimulation, TLR3 forces intestinal epithelial cells (IECs) to express both IL-15 and RAE1, which promote mucosal damage by activating intraepithelial lymphocytes (IELs), in particular CD8αα+ T cells, engaging their NKG2D receptor [21]. In this scenario, Tada and colleagues have shown that probiotics belonging to Lactobacillus strains are able to reduce the levels of IL-15 and RAE-1, and at the same time to increase the level of IL-10 in the intestine, performing immunomodulatory activities [22] (Figure 1).

Cigarette smoke

Celiac Disease

CONCLUDING REMARKS

AUTHOR CONTRIBUTIONS