Th17 cells regulate the progress of anti-NMDAR encephalitis

Am J Transl Res. 2022 Sep 15;14(9):6268-6276. eCollection 2022.

Abstract

Objective: To explore the mechanism of immune regulation of Th17 in anti-NMDAR encephalitis disease.

Methods: This is a retrospective study with 83 subjects included. All subjects were admitted to the Second Affiliated Hospital of Hainan Medical University from April 2018 to May 2021, including 35 patients with anti-NMDA encephalitis in an encephalitis group, and 48 patients with non-inflammatory central neuropathy in a control group. The cerebrospinal fluid (CSF) and blood samples were collected from two groups of patients, and the changes of Th17 cell, immunophenotypic characteristics, differentiation pathways and the effect were analyzed accordingly. Peripheral blood mononuclear cells (PBMCs) from patients with anti-NMDAR encephalitis were isolated and treated with different cytokines, namely IL-1β+IL-6 group, IL-1β+IL-23 group, IL-6+IL-23 group, IL-1β+IL-23+IL-6 group and TGF-β group. After co-culture, the proportion of Th17 cells and the expression level of Th17 cell-specific transcription factor RORγt mRNA were examined.

Results: Th17 cells in CSF were dramatically uplifted in the encephalitis group. In terms of cell phenotype, the percentages of CD62L and CCR7 expressions in Th17 cell phenotype were significantly increased in the encephalitis group. IL-1β, IL-6, IL-7 and IL-23 mRNA in PBMCs and IL-1β, IL-6, IL-7 and IL-23 in serum were remarkably uplifted in the encephalitis group. The mRNA levels of Th17 and Th17 cell-specific transcription factor RORγ T were the highest in the IL-1β+IL-6+IL-23 group but the lowest in the TGF-β group. Th17 in CSF of patients with poor prognosis was notably higher than that of those with good prognosis.

Conclusion: The proportion of Th17 cells in patients with NMDAR encephalitis and the expressions of corresponding differentiation promoting cytokines were increased, and Th17 is closely associated with patients' treatment and prognosis. Th17 cells play crucial roles in tumorigenesis and progression of anti-NMDAR encephalitis.

Keywords: IL-17; NMDAR; Th17 cell; autoimmune encephalitis; immune regulation.