Investigation of immune cell differentiation and function is limited by shortcomings of suitable and scalable experimental systems. Here we show that an estrogen–regulated form of HOXB8 that is retrovirally delivered into mouse bone marrow cells can be used along with FLT3 ligand to conditionally immortalize early hematopoietic progenitor cells (Hoxb8–FL). Hoxb8–FL cells have lost self–renewal capacity and megakaryocyte/ erythroid lineage potential, but sustain myeloid and lymphoid potential. Hoxb8–FL cells differentiate in vitro and in vivo into different myeloid and lymphoid cell types, including macrophages, granulocytes, dendritic cells and B– and T–lymphocytes, which are phenotypically and functionally indistinguishable from their primary counterparts. Quantitative in vitro cell lineage potential assays implicate that myeloid and B–cell potential of Hoxb8–FL cells is comparable to primary lymphoid–primed multipotent progenitors, while T–cell potential is comparatively reduced. Given the simplicity and unlimited proliferative capacity of Hoxb8–FL cells, this system provides unique opportunities to investigate cell differentiation and immune cell functions.

Toll-like receptors (TLRs) are expressed on innate immune cells and trigger inflammation upon detection of pathogens and host tissue injury. TLR-mediated proinflammatory-signaling pathways are counteracted by partially characterized anti-inflammatory mechanisms that prevent exaggerated inflammation and host tissue damage as manifested in inflammatory diseases. We biochemically identified a component of TLR-signaling pathways, A20-binding inhibitor of NF-κB (ABIN1), which recently has been linked by genome-wide association studies to the inflammatory diseases systemic lupus erythematosus and psoriasis. We generated ABIN1-deficient mice to study the function of ABIN1 in vivo and during TLR activation. Here we show that ABIN1-deficient mice develop a progressive, lupus-like inflammatory disease characterized by expansion of myeloid cells, leukocyte infiltrations in different parenchymatous organs, activated T and B lymphocytes, elevated serum Ig levels, and the appearance of autoreactive antibodies. Kidneys develop glomerulonephritis and proteinuria, reflecting tissue injury. Surprisingly, ABIN1-deficient macrophages exhibit normal regulation of major proinflammatory signaling pathways and mediators but show selective deregulation of the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) and its target genes, such as colony-stimulating factor 3 ( Csf3 ) , nitric oxide synthase, inducible (Nos2 ), and S100 calcium-binding protein A8 ( S100a8 ). Their gene products, which are intimately linked to innate immune cell expansion (granulocyte colony-stimulating factor), cytotoxicity (inducible nitric oxide synthase), and host factor-derived inflammation (S100A8), may explain, at least in part, the inflammatory phenotype observed. Together, our data reveal ABIN1 as an essential anti-inflammatory component of TLR-signaling pathways that controls C/EBPβ activity.

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Unlike birds and mammals, many teleosts have homomorphic sex chromosomes and changes in the chromosome carrying the sex-determining locus, termed “turnovers”, are common. Recent turnovers allow studies of several interesting questions. One question is whether the new sex-determining regions evolve to become completely non-recombining, and if so, how and why. Another is to test the prediction that evolutionary changes that benefit one sex will accumulate in the newly sex-linked region. To study these questions, we analyzed the genome sequences of two seahorse species of the Syngnathidae, a fish group in which many species evolved a unique structure, the male brood pouch. We find that both seahorse species have XY sex chromosome systems, and their sex chromosome pairs are not homologs, implying that at least one turnover event has occurred. The Y-linked regions respectively occupy 63.9% and 95.1% of the entire chromosome of the two species, and do not exhibit extensive sequence divergence with their X-linked homologs. We find evidence for occasional recombination between the extant sex chromosomes that may account for their homomorphic pattern. We argue that these Y-linked regions did not evolve by recombination suppression after the turnover. Instead, it can be explained by the ancestral nature of low crossover rate at the corresponding chromosome location. With such an ancestral crossover landscape, a turnover can instantly create an extensive Y-linked region. Finally, we investigate the adaptive evolution of male pouch related genes after they become Y-linked in the seahorse.