PD-1+CXCR5−CD4+T cells are correlated with the severity of systemic lupus erythematosus

Abstract

Objectives PD-1+CXCR5−CD4+T peripheral helper (Tph) cells, a recently identified T cell subset, are proven to promote B cell responses and antibody production in rheumatoid arthritis, but their role in the pathogenesis of SLE is unknown. We explored the role of Tph in lupus disease development. Methods This cohort study included 68 patients with SLE and 41 age- and sex-matched healthy individuals. The frequency of PD-1+CXCR5−CD4+T cells was analysed in peripheral blood by flow cytometry. Inducible T-cell costimulator, CD38, MHC-II, IL-21, CXCR3 and CCR6 expression were measured in Tph cells. Comparisons between the two groups were performed, and correlations between Tph cells and other parameters were investigated. Results We revealed a markedly expanded population of Tph cells (8.31 ± 5.45 vs 2.86 ± 1.31%, P < 0.0001) in the circulation of patients with SLE (n = 68), compared with healthy controls (n = 41). Tph cells were much higher in the active group than in the inactive group (14.21 ± 5.21 vs 5.49 ± 2.52%, P < 0.0001). Tph cells were significantly associated with SLEDAI score (r = 0.802), ESR (r = 0.415), IgG (r = 0.434), C3 (r = −0.543), C4 (r = −0.518) and IL-21 level (r = 0.628), and ANA titre (r = 0.272). Furthermore, Tph cells were much higher in lupus patients with arthritis, nephritis, rash, alopecia, pleuritis, pericarditis and haematological involvement. Tph cells were associated with CD138+/CD19+ plasma cells (r = 0.518). Furthermore, MHC-II, inducible T-cell costimulator, CD38, and IL-21 expression were all higher in Tph cells from SLE patients compared with healthy controls. CXCR3+CCR6−Tph (Tph1) cells were expanded in the SLE patients. Conclusion Our data show that relative number of Tph cells is correlated with disease measures in patients with SLE, suggesting an important role in lupus disease development.

Follicular helper T cells in type 1 diabetes

“…In line with this observation, the titers of islet autoantibodies were gradually decreased and seroconversion occurred in some patients with a long duration of T1D. 58,59 Whether Tph cells have a role in the pathogenesis of T1D requires further studies. 51 Meanwhile, the number of TFR cells were significantly decreased in T1D patient and first-degree relatives (FDR) of T1D patients, which could be reversed by rituximab treatment.…”

Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases

“…15 Similarly, cTph cells coexpressing other activation markers, such as CD38 and MHC class II, were increased in patients with systemic lupus erythematosus (SLE). [27][28][29] The frequency of cTph cells in SLE is positively correlated with anti-dsDNA titers, disease activity scores such as SLEDAI, and the frequencies of plasma cells/plasmablasts. [27][28][29] cTph cells in SLE exhibited B cell helper activities by producing IL-21, 29 IL-10, and succinate.…”

The IL‐12‐STAT4 axis in the pathogenesis of human systemic lupus erythematosus

“…For example, in inflamed synovial tissues in rheumatoid arthritis, CD4 + T cells that lack CXCR5 but express PD-1 hi and CCR2 (named peripheral helper T cells: Tph) induce memory B cells to differentiate into ASCs in a manner dependent on IL-21 and ICOS [59]. Recent studies showed an increase of CXCR5 − PD-1 hi Tph cells expressing CXCR3 in the blood of active SLE patients [60,61]. Similar to Tph cells in inflamed synovial tissues in rheumatoid arthritis, Lin et al showed that the blood Tph cells in SLE expressed high IL-21 and IFN-γ, and the frequency in the blood correlated with disease activity [60].…”

“…Recent studies showed an increase of CXCR5 − PD-1 hi Tph cells expressing CXCR3 in the blood of active SLE patients [60,61]. Similar to Tph cells in inflamed synovial tissues in rheumatoid arthritis, Lin et al showed that the blood Tph cells in SLE expressed high IL-21 and IFN-γ, and the frequency in the blood correlated with disease activity [60]. By contrast, Caielli et al showed that CXCR3 + Tph cells in SLE patients expressed high IL-10, IFN-γ, and succinate, but no IL-21 or CXCL13, and provided help to B cells in a manner dependent on IL-10 and succinate [61].…”

“…Similar to Tph cells in inflamed synovial tissues in rheumatoid arthritis, Lin et al. showed that the blood Tph cells in SLE expressed high IL‐21 and IFN‐γ, and the frequency in the blood correlated with disease activity . By contrast, Caielli et al.…”