CD19+IL-10+ regulatory B cells induced by IL-12p35 regulates functional T-cell subsets in patients with immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is a condition characterized by immune-mediated platelet loss due to excessive destruction and/or insufficient production. IL-12p35 is involved in autoimmune uveitis; however, its role in ITP remains unknown. In the study, CD19+ B and CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) of patients with ITP and healthy individuals. CD4+CD25- T cells were cocultured with the CD19+ B cells treated with anti-IL-12p35 antibody or IL-12p35 recombinant protein. The impact of IL-12p35 on CD19+ B cells was assessed by enzyme-linked immunosorbent assay, Western blotting, quantitative real-time PCR and flow cytometry. PBMCs from patients with ITP showed lower proportions of IL-10+CD19+ B cells and decreased mRNA levels of IL-12p35-coding gene IL12A than those from healthy individuals. Anti-IL-12p35 antibody-treated CD19+ B cells could reduce the population of IL-10+ in CD19+ B cells and regulate the differentiation of CD4+CD25- T cells, while recombinant IL-12p35 demonstrated the opposite effects. Moreover, the increased IL-10+ B-cell population and HIF-1α expression in CD19+ B cells induced by recombinant IL-12p35 were reversed by HIF-1α and JAK2/STAT3 inhibitors. In conclusion, CD19+IL-10+ B cells induced by IL-12p35 regulate CD4+ T-cell subsets in patients with ITP via the JAK2/STAT3/HIF-1α signalling pathway.