Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice

摘要

APCs are essential for innate and adaptive immunity as well as self-immune tolerance. Here, we show that the Cap'n'collar member Bach1 regulates the generation of APCs, specifically macrophages and dendritic cells, in mice. The impaired APC development in Bach1 -/-mice was accompanied by defects in downstream T-cell responses and partial protection from experimental autoimmune encephalomyelitis. Genomewide analyses identified a panel of Bach1 target genes and ablation of the direct Bach1 target gene HO-1 exacerbated the impaired APC development observed in Bach1 -/- mice. This was attributed to the impaired ability of HO-1 -/-Bach1 -/-double mutants to produce upstreamAPC progenitor cells, including common myeloid progenitor (CMP)-Flk2 +. By contrast, we observed an increase in hematopoietic stem-progenitor cells (HSPCs) in these mice, suggesting a developmental block in the progression of HSPCs to CMP-Flk2 + and subsequently APCs.