Cellular origin of IFN-gamma essential for hair cycle in normal skin

Hair growth abnormalities in mice usually are accompanied by histologic abnormalities as well. Recently, however, we reported a mouse model in which an arrest of the hair cycle and diffuse shedding of the hair without pathologic features induced alopecia in interferon-gamma(-/-) (IFN-gamma(-/-)) C57BL/6 (B6) mice. Here, we explored the cellular origin of IFN-gamma. When bone marrow from IFN-gamma(-/-) B6 mice was transplanted into lethally irradiated IFN-gamma(+/+) B6 mice, the level of IFN-gamma mRNA expression in the skin or peripheral blood mononuclear cells (PBMCs) of recipient mouse was markedly reduced, suggesting that IFN-gamma is normally produced by bone marrow-derived cells. Although severe combined immunodeficiency (SCID) mice lack mature T cells and B cells, IFN-gamma-dependent hair regrowth was induced in SCID mice by depilation, which caused alopecia in IFN-gamma(-/-) B6 mice. Consistently, IFN-gamma mRNA expression in the skin or PBMC from SCID mice was comparable to that from their genetic counterpart (BALB/c mice), suggesting IFN-gamma production by non-T cells. RT-PCR analyses after separation of PBMC from SCID mice into eight fractions by a cell sorter revealed that Mac-1(+) cells were the major origin of IFN-gamma.