SummaryDifferentiation and proliferation of haematopoietic progenitor cells occur in intimate contact with the bone marrow microenvironment which is composed of stromal cells and extracellular matrix proteins. MOP3 (also known as brain and muscle Arnt-like protein-1, BMAL1), a master regulator of circadian rhythm, plays important roles in the regulation of cell differentiation and general physical functions. In the present studies, MOP3-deficient mice had significantly reduced levels of B cells in the peripheral blood, spleen and bone marrow compared MOP3 +/-or MOP3
SummaryMOP3 (also known as BMAL1), a master regulator of circadian rhythm, plays important roles in the regulation of cell differentiation and general physical functions. In the present studies, MOP3 deficient mice had significantly reduced body weight and showed remarkable mortality around six months of age. The levels of AST, ALT, BUN, or UREA in the blood of about four month-old MOP3 )/) mice were significantly higher than MOP3 +/) or MOP3 +/+ littermates. However, no apparent pathological changes in the livers, hearts, lungs or kidneys of about four month-old MOP3 )/) mice were observed. In addition, altered levels of white blood cells, lympgocytes, and platelets in peripheral blood of MOP3 )/) mice were detected. The results presented herein with MOP3-deficient mice offered the basic principle for the essential roles of MOP3 in keeping normal survival abilities in mice. This study may have significant clinical impacts on the consideration about the abnormality of circadian rhythms and sleeping disorders caused physical and metabolism dysfunctions as well as the mortality.Abbreviations: ALT -alanine aminotransferase; ARNT -aryl hydrocarbon receptor nuclear translocator; AST -asparate aminotransferase; bHLH -basic-helix-loop-helix domain; BMAL1 -brain and muscle Arnt-like protein-1; CLOCK -product of the clock locus in mice; HIF -hypoxia-inducible factor; PAS -PER-ARNT-SIM homology domain; SGPT -serum glutamic pyruvic transaminase; SGOT -serum glutamic oxalocetic transaminase
The immune regulatory function of macrophages (Møs) in mixed chimeras has not been determined. In the present study, with a multi-lineage B6-to-BALB/c mixed chimeric model, we examined the ability of donor-derived splenic Møs in the induction of regulatory T cells (Treg). B6 splenic Møs from mixed chimeras induced significantly less cell proliferation, more IL-10 and TGFb, and less IL-2 and IFN-c productions of CD4 + T cells from BALB/c mice than naive B6 Møs did, whereas they showed similar stimulatory activity to the third part C3H CD4 + T cells. Importantly, highly purified donor F4/80 + CD11c À Møs efficiently induced recipient CD4 + Foxp3 + Treg cells from CD4 + CD25 À Foxp3 À T cells. Furthermore, donor Møs of mixed chimeras produced more IL-10 and less IFN-c than those of naive mice when cultured with BALB/c but not the third party C3H CD4 + T cells. Induction of recipient CD4 + Treg cells by donor Møs was significantly blocked by anti-IL-10, but not by anti-TGF-b mAb. Therefore, donor Møs have the ability to induce recipient CD4 + Foxp3 + Treg cells in a donor antigen-specific manner, at least partially, via an IL-10-dependent pathway. This study for the first time showed that, in mixed allogeneic chimeras, donor Møs could be specifically tolerant to recipients and gained the ability to induce recipient but not the third party Foxp3 + Treg cells. Whether this approach is involved in transplant immune tolerance needs to be determined.
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