Activated circulating T follicular helper cells and skewing of T follicular helper 2 cells are down-regulated by treatment including an inhaled corticosteroid in patients with allergic asthma

Abstract

Background: CXCR5⁺ T follicular helper (T_FH) cells primarily promote B cells to produce an antigen-specific antibody through germinal centers (GCs). T_FH cells exist in circulation, and circulating(c) T_FH2 cells, a subset of cT_FH cells, are able to help naïve B cells produce IgE in healthy individuals. Conversely, IL-10-producing regulatory B (Breg) cells inhibit an accelerated immune response.

Methods: We investigated the roles of cT_FH cells and cBreg cells based on a T_H2 response in patients with atopic asthma (AA). Thirty-two patients with AA and 35 healthy volunteers (HV) were enrolled. We examined cT_FH cells including their subsets, their expression of ICOS and PD-1, and cBreg cells by flow cytometry and their associations with clinical biomarkers. Plasma levels of CXCL13, which is a counterpart of CXCR5, were also measured using ELISA.

Results: In patients with AA, cT_FH2 cells were increased and cT_FH1 cells were decreased compared with those in HV. The expression levels of ICOS on cT_FH and their subset cells were elevated and Breg cells were greatly decreased. The plasma levels of CXCL13 in patients with AA were significantly elevated and correlated well with the cT_FH2/cBreg ratio. These cells were examined in 10 patients AA before and after inhaled corticosteroid (ICS) treatment. Interestingly, the percentages and numbers of T_FH2 and ICOS⁺ cT_FH cells declined after ICS treatment together with improvements in symptoms and clinical biomarkers.

Conclusions: The percentages and numbers of cT_FH2 and ICOS⁺ cT_FH cells might be useful as biomarkers of T_H2 typed airway inflammation in patients with AA.

Keywords: CXCL13; ICS; IgE; Regulatory B cell; T follicular helper cell.