Aberrant expansion of circulating CD4⁺CXCR5⁺CCR7^loPD1^hi Tfh precursor cells in idiopathic inflammatory myopathy

Abstract

Objective To determine circulating follicular T helper (Tfh) cell precursor and its relationship with clinical characteristics in idiopathic inflammatory myopathy (IIM). Methods The study population included 47 patients with IIM and 30 healthy controls. Circulating CD4+CXCR5+CCR7loPD‐1hi T cells and intracellular interleukin (IL)‐21 were assessed by flow cytometry. Serum IL‐21 levels were measured by enzyme‐linked immunosorbent assay. The disease activity was evaluated using myositis disease activity assessment visual analog scales (VAS) as well as muscle and physician global assessment (PGA). Results The percentage of the CCR7loPD‐1hi subset cells within CD4+CXCR5+ T cells was significantly increased in patients with IIM compared to that in healthy controls (14.3 ± 6.5 vs 11.4 ± 2.6, P = .009). Patients with higher percentages of CCR7loPD‐1hi subsets presented with higher PGA VAS (P = .000), muscle VAS (P = .000), as well as serum creatinine kinase (CK) levels (P = .000) than those with lower percentages of CCR7loPD‐1hi subsets. IL‐21 expression significantly increased in CD4+CXCR5+CCR7loPD‐1hi T cells in patients with IIM compared to that in healthy controls (26.07 ± 7.38 vs 19.25 ± 5.67, P = .001). Meanwhile, both the CCR7loPD‐1hi subset and intracellular IL‐21 expression in IIM patients showed significantly positive correlation with PGA VAS, muscle VAS and serum CK levels. Circulating CD4+CXCR5+CCR7loPD‐1hi T cells and intracellular IL‐21 decreased significantly when disease was improved (P = .018; P = .028). Conclusion The percentage of circulating CCR7loPD‐1hi subset among total CD4+CXCR5+ T cells and intracellular IL‐21 expression expanded and showed significant correlation with disease activity in IIM. The circulating follicular helper T cell precursor may be involved in the pathogenesis, especially muscle injury in IIM.

Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy

“…Moreover, we characterized the immune microenvironment of IIM. Consistent with previous findings, there was a substantial infiltration of pro-inflammatory immune cells in the IIM group (follicular helper T cells, gamma delta T cells, and M1 macrophages) and a clear lack of suppressive inflammatory cells (Tregs) compared to the HC group ( 65 – 67 ). Correlation analysis revealed that key genes were linked to multiple immune-infiltrating cells, indicating that key genes may be involved in the progression of IIM by regulating immune cells.…”

Biomarkers of disease activity in dermatomyositis

“…It has also been revealed that higher percentages of CD4þCXCR5þCCR7loPD-1hi T cells were associated with higher disease activity scores assessed by PGA and higher serum creatine kinase levels. In addition, the percentage of circulating CD4þCXCR5þ CCR7loPD-1hi T cells decreased significantly after successful treatment [25]. These findings indicate that CD4þCXCR5þCCR7loPD-1hi T cells may be a disease activity marker in polymyositis/dermatomyositis patients.…”

“…Moreover, several studies attempted to identify new T-cell subsets in myositis patients and correlated the subsets' abnormalities with disease activities. Zhang et al [25] investigated a Tfh cell-like circulating T-cell subsets, CD4þCXCR5þCCR7loPD-1hi T cells, in polymyositis and dermatomyositis patients and found that this subset of T cells was significantly increased in polymyositis/dermatomyositis patients. It has also been revealed that higher percentages of CD4þCXCR5þCCR7loPD-1hi T cells were associated with higher disease activity scores assessed by PGA and higher serum creatine kinase levels.…”

T follicular helper cells and T peripheral helper cells in rheumatic and musculoskeletal diseases

“…Multiple studies have reported an increase in circulating Tfh cells in patients with idiopathic inflammatory myopathies, particularly Tfh2 and Tfh17 14 79–81. In the affected muscle tissue of patients with dermatomyositis, infiltration of Tph cells and clustering of B cells around it have been observed, suggesting that Tph cells may be involved in the enhancement and persistence of autoimmune responses at peripheral inflammatory sites 82.…”