Expansion of IL-6+ Th17-like cells expressing TLRs correlates with microbial translocation and neurological disabilities in NMOSD patients

Abstract

Different microbial antigens, by signaling through toll-like receptors (TLR), may contribute to Th17-mediated autoimmune diseases, such as neuromyelitis optica spectrum disorder (NMOSD). The objective of this study was to determine the proportion of different Th17-like cell subsets that express TLR in NMOSD patients. For this study, the frequency of different Th17 cell subsets expressing TLR subsets in healthy individuals (n=20) and NMOSD patients (n=20) was evaluated by cytometry. The peripheral levels of soluble CD14 (sCD14) and cytokines were determined by ELISA. Our results demonstrated that the proportion of peripheral CD4⁺ T cells expressing TLR2, 4 and 9 was significantly higher in NMOSD samples than in healthy subjects. In NMOSD, these cells are CD28⁺PD-1^-CD57^- and produce elevated levels of IL-17. Among different TLRs⁺ Th17-like subsets, the proportion of those that co-express IL-17 and IL-6 was significantly higher in NMOSD patients, which was positively correlated with sCD14 levels and EDSS score. By contrast, the percentage of TLRs⁺Treg17 cells (IL-10⁺IL-17⁺) was negatively related to sCD14 and the severity of NMOSD. In conclusion, the expansion of peripheral IL-6-producing TLR⁺ Th17-like cells in NMOSD patients was associated with both bacterial translocation and disease severity.

Keywords: CD14; NMOSD; Th17 phenotype; Toll-like receptor.