Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice.
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 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.
Department of Biology, California Institute of Technology, Pasadena, CA 90227, USA.
Alex Yick-Lun
AY
So
Yvette
Y
Garcia-Flores
Aarathi
A
Minisandram
Ayana
A
Martin
Konstantin
K
Taganov
Mark
M
Boldin
David
D
Baltimore
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000502:physiology*; D007111:Immunity, Cellular / Q000276:immunology*; D007114:Immunization; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D015415:Biomarkers; D008565:Membrane Proteins; D012333:RNA, Messenger; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse