Gut Microbiome and Bile Acid Metabolism Induced the Activation of CXCR5+ CD4+ T Follicular Helper Cells to Participate in Neuromyelitis Optica Spectrum Disorder Recurrence

Abstract

From the perspective of the role of T follicular helper (Tfh) cells in the destruction of tolerance in disease progression, more attention has been paid to their role in autoimmunity. To address the role of Tfh cells in neuromyelitis optica spectrum disorder (NMOSD) recurrence, serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of the Tfh cells on B-cell-mediated humoral immunity. We evaluated the immunobiology of the CXCR5+CD4+ Tfh cells in 46 patients with NMOSD, including 37 patients with NMOSD with an annual recurrence rate (ARR) of<1 and 9 patients with NMOSD with an ARR of ≥1. Herein, we reported several key observations. First, there was a lower frequency of circulating Tfh cells in patients with an ARR of<1 than in those with an ARR of ≥1 (P< 0.05). Second, the serum CXCL13 levels were downregulated in individuals with an ARR<1 (P< 0.05), processing the ability to promote Tfh maturation and chemotaxis. Third, the level of the primary bile acid, glycoursodeoxycholic acid (GUDCA), was higher in patients with NMOSD with an ARR of<1 than in those with NMOSD with an ARR of ≥1, which was positively correlated with CXCL13. Lastly, the frequency of the Tfh precursor cells decreased in the spleen of keyhole limpet haemocyanin-stimulated animals following GUDCA intervention. These findings significantly broaden our understanding of Tfh cells and CXCL13 in NMOSD. Our data also reveal the potential mechanism of intestinal microbiota and metabolites involved in NMOSD recurrence.

Correlation of GABA+ levels in the medial prefrontal cortex and circulating follicular helper T cells in neuromyelitis optica spectrum disorder patients with cognitive impairment

“…In addition, Tfh cells were found to contribute to the pathophysiology in an NMOSD mouse model, and Tfh cell depletion via abrogating ICOS/ICOS-L signaling ameliorated astrocytopathy (Yick et al, 2023). Tfh cells were also found positively correlated with severity (Monteiro et al, 2019; and relapse (Cheng et al, 2022;Fan et al, 2016;Zhao et al, 2017) in NMOSD patients.…”

“…In addition, Tfh cells were found to contribute to the pathophysiology in an NMOSD mouse model, and Tfh cell depletion via abrogating ICOS/ICOS‐L signaling ameliorated astrocytopathy (Yick et al., 2023 ). Tfh cells were also found positively correlated with severity (Monteiro et al., 2019 ; Yang et al., 2021 ) and relapse (Cheng et al., 2022 ; Fan et al., 2016 ; Zhao et al., 2017 ) in NMOSD patients. Fan and colleagues concurrently confirmed the positive correlation of percentages of CCR7‐ and CCR7‐ICOS + memory Tfh cells with AQP4‐IgG level (Fan et al., 2016 ).…”

Gut microbiota: a new insight into neurological diseases

“…[84] Variations of several gut microorganisms, especially Vagococcus and Anaerobiospirillum spp., and their metabolites (e.g., bile acids), correlated with NMOSD recurrence through CXCL13-induced activation of the CXCR5+ CD4+ follicular T helper cell pathway. [85] Gut microbiota and MG…”

“…In addition, a study of sigmoid mucosal biopsies from NMOSD patients proposed that mucosal microbiota imbalance and inflammatory cell activation allowed pathogens to cross the damaged intestinal barrier and participate in the pathogenesis of NMOSD [84] . Variations of several gut microorganisms, especially Vagococcus and Anaerobiospirillum spp., and their metabolites (e.g., bile acids), correlated with NMOSD recurrence through CXCL13-induced activation of the CXCR5+ CD4+ follicular T helper cell pathway [85] …”

Association Between Gut Microbiota and Osteoarthritis: A Review of Evidence for Potential Mechanisms and Therapeutics

“…( Shan et al., 2017 ) found that the percentages of CXCR5+CD4+ Tfh cells in OA patients were significantly higher than that in the healthy control group. Interestingly, a novel insight showed that the activation of CXCR5+CD4+ Tfh cells could be induced by gut microbiota and bile acid metabolism ( Cheng et al., 2022 ). Segmented filamentous bacteria, a gut-residing specie, has been demonstrated to drive autoimmune arthritis via Th17 cells ( Wu et al., 2010 ), which can be accumulated in the synovial fluid and synovial tissue of OA patients ( Chabaud et al., 1999 ; Qi et al., 2016 ).…”