Early Treatment of Interleukin-33 can Attenuate Lupus Development in Young NZB/W F1 Mice.

Fatin Nurizzati Mohd Jaya,Godfrey Chi-Fung Chan,Zhongyi Liu

doi:10.3390/cells9112448

Abstract

Interleukin-33 (IL-33), a member of the IL-1 cytokine family, has been recently associated with the development of autoimmune diseases, including systemic lupus erythematosus (SLE). IL-33 is an alarmin and a pleiotropic cytokine that affects various types of immune cells via binding to its receptor, ST2. In this study, we determine the impact of intraperitoneal IL-33 treatments in young lupus, NZB/W F1 mice. Mice were treated from the age of 6 to 11 weeks. We then assessed the proteinuria level, renal damage, survival rate, and anti-dsDNA antibodies. The induction of regulatory B (Breg) cells, changes in the level of autoantibodies, and gene expression were also examined. In comparison to the control group, young NZB/W F1 mice administered with IL-33 had a better survival rate as well as reduced proteinuria level and lupus nephritis. IL-33 treatments significantly increased the level of IgM anti-dsDNA antibodies, IL-10 expressing Breg cells, and alternatively-induced M2 macrophage gene signatures. These results imply that IL-33 exhibits a regulatory role during lupus onset via the expansion of protective IgM anti-dsDNA as well as regulatory cells such as Breg cells and M2 macrophages.

Highlights

Interleukin-33 (IL-33) belongs to the inflammatory IL-1 cytokine family [1]
We found that the administration of IL-33 starting from the age of 6 weeks significantly reduced proteinuria level and mortality rate
We found that early

Summary

Introduction

Interleukin-33 (IL-33) belongs to the inflammatory IL-1 cytokine family [1]. Higher expression of IL-33 has been reported in the barrier tissues, such as the epithelial and endothelial presumably due to its role as a tissue-derived alarmin and damage-associated molecular pattern (DAMP) of the immune system [1]. Upon tissue damage and necrosis, the active full length of IL-33 is released and signals through a heterodimeric receptor complex, ST2, and interleukin-1 receptor accessory protein (IL-1RAcP) [3]. IL-33 signaling leads to the downstream activation of nuclear factor (NK)-κB and increased production of T-helper 2 (Th2) cytokines such as IL-4, IL-5, and IL-13 [4,5]. IL-33 can act on numerous immune cells including T cells (Tregs), T helper (Th) 2 cells, mast cells, and type 2 innate lymphoid (ILC2s) cells [6,7]. The involvement of IL-33 in autoimmune diseases such as in rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), and systemic lupus erythematosus (SLE) has been described [9]

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