Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice
Copyright policy )Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice
AbstractAPCs 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 upstream APC 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.
- Beckman Research Institute United States
- California Institute of Technology United States
- City Of Hope National Medical Center United States
Male, Mice, Knockout, Immunity, Cellular, Encephalomyelitis, Autoimmune, Experimental, Gene Expression Profiling, Blotting, Western, 610, Antigen-Presenting Cells, Membrane Proteins, Autoimmunity, Hematopoietic Stem Cells, Immunoenzyme Techniques, Mice, Inbred C57BL, Mice, Basic-Leucine Zipper Transcription Factors, Animals, Female, Immunization, Biomarkers, Heme Oxygenase-1, Oligonucleotide Array Sequence Analysis
Male, Mice, Knockout, Immunity, Cellular, Encephalomyelitis, Autoimmune, Experimental, Gene Expression Profiling, Blotting, Western, 610, Antigen-Presenting Cells, Membrane Proteins, Autoimmunity, Hematopoietic Stem Cells, Immunoenzyme Techniques, Mice, Inbred C57BL, Mice, Basic-Leucine Zipper Transcription Factors, Animals, Female, Immunization, Biomarkers, Heme Oxygenase-1, Oligonucleotide Array Sequence Analysis
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