Differential requirement for Hoxa9 in the development and differentiation of B, NK, and DC-lineage cells from Flt3+ multipotential progenitors

BMC Immunology

Kay L Medina¹  Mariya B Shapiro¹  Joseph J Dolence¹  Kimberly Gwin¹ 

[1] Department of Immunology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

关键词: Development;    DC;    NK-cell;    B-cell;    IL-7R;    Flt3;    Hoxa9;   

Others  :  1077842
DOI  :  10.1186/1471-2172-14-5

 received in 2012-10-16, accepted in 2013-01-25,  发布年份 2013

【 摘 要 】

Hoxa9 is a homeodomain transcription factor important for the generation of Flt3+hiIL-7R- lymphoid biased-multipotential progenitors, Flt3+IL-7R+ common lymphoid progenitors (CLPs), and B cell precursors (BCP) in bone marrow (BM). In addition to B-cell, Flt3+IL-7R+ CLPs possess NK and DC developmental potentials, although DCs arise from Flt3+IL-7R- myeloid progenitors as well. In this study, we investigated the requirement for Hoxa9, from Flt3+ or Flt3- progenitor subsets, in the development of NK and DC lineage cells in BM. Flt3+IL-7R+Ly6D- CLPs and their Flt3+IL-7R+Ly6D+ B lineage-restricted progeny (BLP) were significantly reduced in hoxa9−/− mice. Interestingly, the reduction in Flt3+IL-7R+ CLPs in hoxa9−/− mice had no impact on the generation of NK precursor (NKP) subsets, the differentiation of NKP into mature NK cells, or NK homeostasis. Similarly, percentages and numbers of common dendritic progenitors (CDP), as well as their plasmacytoid or conventional dendritic cell progeny in hoxa9−/− mice were comparable to wildtype. These findings reveal distinct requirements for Hoxa9 or Hoxa9/Flt3 molecular circuits in regulation of B versus NK and DC development in BM.

【 授权许可】

   
2013 Gwin et al.; licensee BioMed Central Ltd.

【 图 表 】

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