Secreted cyclophilin A regulates the development of adaptive immune response by modulating B and T cell functional activity in experimental models in vivo and in vitro.

Abstract

Cyclophilin A (CypA) is a member of the isomerase family; in the secreted form, it acts as a chemoattractant and pro-inflammatory factor, orchestrating the development of the local inflammatory response. In this work, we studied the role of secreted CypA in regulating an adaptive immune response. Our findings showed that injections of recombinant human CypA (rhCypA) into mice induced nonspecific activation of T and B cells in vivo that resulted in stimulation of the humoral immune response and suppression of the cellular immune response to model antigens. In vitro, rhCypA-induced activation and proliferation of nonprimed B cells, acted as a co-mitogen for CD40-stimulated B cells and improved their functions as antigen-presenting cells by regulating the expression of CD86 and the major histocompatibility complex (MHC) class II. These immunoregulatory effects of rhCypA could be, at least partially, implemented by modulating the expression of its receptor CD147 on B cells. Having no effects on nonprimed T cells, rhCypA boosted the proliferation of T cells activated through a T cell receptor and enhanced their cytotoxic activity. Here, we proposed secretory CypA as a regulator of the adaptive immune response and provided an insight into CypA-mediated remodeling of T and B cell functional activity.