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

APCs are essential for innate and adap-tive immunity as well as self-immune tolerance. Here, we show that the Cap’n’collar member Bach1 regulates the generation of APCs, specifically macro-phages 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 autoim-mune encephalomyelitis. Genomewide analyses identified a panel of Bach1 tar-get genes and ablation of the direct Bach1 target gene HO-1 exacerbated the im-paired APC development observed in Bach1/ mice. This was attributed to the impaired ability of HO-1/Bach1/ double mutants to produce upstream APC progenitor cells, including common my-eloid progenitor (CMP)–Flk2. By con-trast, we observed an increase in hemato-poietic stem-progenitor cells (HSPCs) in these mice, suggesting a developmental block in the progression of HSPCs to CMP-Flk2 and subsequently APCs. (Blood. 2012;120(12):2428-2437