Inflammatory Arthritis and Bone Metabolism Regulated by Type 2 Innate and Adaptive Immunity.

Yasunori Omata,Taku Saito,Sakae Tanaka,Michael Frech,Mario M Zaiss,Georg Schett

doi:10.3390/ijms23031104

Abstract

While type 2 immunity has traditionally been associated with the control of parasitic infections and allergic reactions, increasing evidence suggests that type 2 immunity exerts regulatory functions on inflammatory diseases such as arthritis, and also on bone homeostasis. This review summarizes the current evidence of the regulatory role of type 2 immunity in arthritis and bone. Key type 2 cytokines, like interleukin (IL)-4 and IL-13, but also others such as IL-5, IL-9, IL-25, and IL-33, exert regulatory properties on arthritis, dampening inflammation and inducing resolution of joint swelling. Furthermore, these cytokines share anti-osteoclastogenic properties and thereby reduce bone resorption and protect bone. Cellular effectors of this action are both T cells (i.e., Th2 and Th9 cells), but also non-T cells, like type 2 innate lymphoid cells (ILC2). Key regulatory actions mediated by type 2 cytokines and immune cells on both inflammation as well as bone homeostasis are discussed.

Highlights

IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
The role of type 1 immune responses has been investigated in terms of their role in inflammation and bone, recent studies revealed that type 2 immunity has regulatory properties on a disease like arthritis, and affects bone metabolism
Type 2 immunity is exerted by T helper 2 (Th2) cells, eosinophils, mast cells, basophils, Th9 cells, and the recently discovered type 2 innate lymphoid cells (ILC2s)

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Host immune responses are exerted by innate and adaptive immune cells. Type 2 immunity is exerted by T helper 2 (Th2) cells, eosinophils, mast cells, basophils, Th9 cells, and the recently discovered type 2 innate lymphoid cells (ILC2s). A third type of immunity is characterized by Th17 cells and type 3 innate lymphoid cells (ILC3s) These immune cells communicate with each other and regulate inflammation to adjust and balance immune responses [1]. In inflammatory diseases such as rheumatoid arthritis (RA) demonstrating proliferative synovitis and bone destruction, innate and adaptive immunity are involved in the pathology [2]. Activated macrophages secrete interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)α, which stimulate synovial fibroblasts to express receptor activator of NF-κB fibroblasts to express of NF-κB ligand (RANKL).

Regulation

Type 2 Innate Lymphoid Cells in Arthritis

Type 2 Immunity and Bone Metabolism

Findings

Conclusions