Sex Differences in monocytes and TLR4 associated immune responses; implications for systemic lupus erythematosus (SLE).

Wei Jiang,Gary Gilkeson

doi:10.7243/2055-2394-1-1

Abstract

It has been shown that TLR7 and TLR9 signaling play a role in SLE pathogenesis. Our recent study revealed that estrogen receptor α knockout mice have impaired inflammatory responses to TLR3, TLR4, TLR7 and TLR9 ligand stimulation in DCs, B cells and whole spleen cells. These findings indicate that estrogen receptor mediated signaling may impact universal TLR responsiveness. Whether estrogen has a direct or indirect effect on TLR responsiveness by immune cells is not clear. There is evidence of a role of TLR4 in SLE disease pathogenesis, such as the kidney damage, the induction of CD40 and autoantibodies, the suppression of regulatory T cells, and the role of pro-inflammatory cytokines (e.g., IL-6, IL-1β, TNF-α) in SLE pathogenesis that can be induced by TLR4-mediated monocyte activation, suggesting that TLR4 and TLR4 responsiveness are also important for SLE disease. This review will focus on TLR4 responses and monocytes, which are understudied in systemic autoimmune diseases such as SLE.

Highlights

Women exhibit stronger cellular-mediated and humoralmediated immune responses compared to men, and a higher risk of autoimmune disease [1]
Our previous study showed that TLR3, TLR4, TLR7 and TLR9 responsiveness was decreased in immune cells from estrogen receptor α knockout mice [14], suggesting that TLR7 responsiveness, but other Tolllike receptor (TLR) responsivenessis modified by estrogen receptor signaling
Dendritic cells (DCs), especially plasmacytoid dendritic cells (pDCs) produce a large amount of IFN-α in response to TLR7and TLR9 ligands, which play an important role in the pathogenesis of systemic lupus erythematosus (SLE) disease [15,16]. pDCsproduce more IFN-α in women than men in response to TLR7 ligands, perhaps due to TLR7 being located on the X chromosome leading to variable responsiveness [8,17]

Summary

Introduction

Women exhibit stronger cellular-mediated and humoralmediated immune responses compared to men, and a higher risk of autoimmune disease [1]. Dendritic cells (DCs), especially pDCs produce a large amount of IFN-α in response to TLR7and TLR9 ligands, which play an important role in the pathogenesis of SLE disease [15,16]. These results suggest that monocytes are activated in vivo, produce pro-inflammatory cytokines (e.g., IL-6), and play a key role in chronic inflammation and disease pathogenesis in SLE [57].

Results

Conclusion