A recent study demonstrated that regulatory B cells (Bregs) play a crucial role in autoimmune diseases. However, the molecular mechanisms underlying the regulatory function of Bregs remain controversial.
In this study, we collected human peripheral blood and utilized mouse autoimmune disease models to identify the frequency and function of Bregs in autoimmune diseases such as IBD and Hashimoto thyroiditis.
We found an increased population of Bregs with promoted suppressive function in autoimmune diseases. Moreover, via gene expression microarrays and flow cytometry, we found that HSP70 expression was significantly up-regulated in Bregs especially in diseases. In vitro and in vivo studies explored that inhibiting HSP70 expression changed the regulatory function of Bregs. Furthermore, adoptively transferred Hsp70 overexpressed B cells effectively rescue diseases. Mechanistically, HSP70 modulated Breg suppressive function via directly producing secreted HSP70 and targeting conventional T cells.
Our findings revealed that HSP70 is a novel factor that moderates Breg function, indicating a viable therapy aimed to enhance Breg-mediated production of HSP70.