The Role of Interferon α in human T peripheral helper cells and T follicular helper cells

Abstract

A strong correlation has been found between the interferon signature and the pathogenic expansion of Tph and Tfh cells in lupus. Still, the roles of the Type I IFN on the expression of transcription factors such as MAF and BCL6, and its role on Tph cells in humans is unclear. Through multiple in vitro approaches, CD4 T cells were activated in the presence of IFNα and other cytokines. We analyze through flow cytometry the expression of PD1, CXCR5, ICOS, and HLA-DR as well as some transcription factors present in Tfh and Tph cells. We also evaluated the production of CXCL13 and IL-21 by ELISA. We found that IFNα affected the expression of some surface markers and transcription factors in human T helper cells; moreover, IFNα up-regulated CXCL13 expression in CD4 T cells. This data provide further support to the idea that type I IFN might be one of the drivers of the expansion of the pathogenic Tfh or Tph cells or the aberrant T and B cell interaction in lupus. This effect may be one of the mechanisms through which emerging therapies that block IFN, such as anifrolumab, may blunt the pathologic immune response in lupus.