Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients.

Aziz Farah Izati,Kah Keng Wong,Che Maraina Che Hussin,Nur Diyana Mohd Shukri,Wan Syamimee Wan Ghazali

doi:10.3389/fimmu.2021.690908

Abstract

The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.

Highlights

Interleukin (IL) is a group of cytokines crucial in regulating immune responses such as inflammation as well as mediating immune cells growth, differentiation, activation, and migration
Among the systemic lupus erythematosus (SLE) patients and healthy controls enrolled in this study (n = 100), two healthy controls were smokers (n = 2/50; 4%) and all SLE patients were non-smokers
We demonstrated that CD3+CD4+ T helper (Th) cells were significantly higher in SLE patients compared with the healthy

Summary

INTRODUCTION

Interleukin (IL) is a group of cytokines crucial in regulating immune responses such as inflammation as well as mediating immune cells growth, differentiation, activation, and migration. IL-17 produced by Th17 cells has been implicated in the pathogenesis of autoimmune diseases including SLE [4]. Cytokine receptors activate intracellular signaling which controls a wide range of biological and clinically relevant functions including inflammatory reactions and the expansion of immune cells. Multiple studies have reported that elevated IL-17 serum levels in SLE patients is associated with higher SLEDAI scores, a parameter to assess SLE disease activities [17,18,19,20], compared with the controls [21,22,23,24,25,26]. The potential associations between these serum cytokines and Th cell subsets with SLE disease activity measured by the SLEDAI-2K scores were examined. Associations of the SLEDAI-2K scores with the clinicodemographical (e.g., age) and immunological (e.g., ANA, antidsDNA) parameters were investigated, and compared with the IL-23/IL-17 axis parameters using multivariate and false discovery rate (FDR) analyses

MATERIALS AND METHODS

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT

ETHICS STATEMENT