IFN regulatory factor 8 represses GM-CSF expression in T cells to affect myeloid cell lineage differentiation.
IFN regulatory factor 8 represses GM-CSF expression in T cells to affect myeloid cell lineage differentiation.
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DOI：
10.4049/jimmunol.1402412
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发表时间：
2015-03-01
期刊：
影响因子：
--
通讯作者：
Liu K
中科院分区：
文献类型：
--
作者：
Paschall AV;Zhang R;Qi CF;Bardhan K;Peng L;Lu G;Yang J;Merad M;McGaha T;Zhou G;Mellor A;Abrams SI;Morse HC 3rd;Ozato K;Xiong H;Liu K
在造血过程中，造血干细胞通过受髓系特异性转录因子严格控制的独特分化程序不断分化为粒细胞和巨噬细胞。IFN调节因子8 （IRF8）零突变的小鼠积累了CD11b+Gr1+髓细胞，其表型和功能类似于肿瘤诱导的髓源性抑制细胞（MDSCs），表明IRF8在髓系细胞谱系分化中起重要作用。然而，IRF8在各种类型的免疫细胞中表达，IRF8在髓细胞谱系分化调控中是内在的还是外在的功能尚不完全清楚。在这里，我们报告了一个有趣的发现，尽管IRF8缺陷小鼠表现出髓系细胞分化失调和CD11b+Gr1+ MDSCs的积累，但令人惊讶的是，仅在髓系细胞中缺乏IRF8的小鼠没有表现出异常的髓系细胞分化。相反，仅在T细胞中缺乏IRF8的小鼠表现出髓细胞分化和MDSC积累的失调。我们进一步证明irf8缺陷T细胞表现出升高的GM-CSF表达和分泌。用GM-CSF处理小鼠增加了MDSC的积累，并且过继性地转移irf8缺陷T细胞，而不是GM-CSF缺陷T细胞，增加了受体嵌合小鼠的MDSC积累。此外，IRF8的过表达降低了T细胞中GM-CSF的表达。我们的数据表明，IRF8除了在髓细胞中作为凋亡调节剂的内在功能外，还可以通过抑制T细胞中GM-CSF的表达来控制髓细胞谱系分化，揭示了免疫系统的适应性免疫成分在体内调节先天免疫细胞骨髓生成的新机制。
During hematopoiesis, hematopoietic stem cells constantly differentiate into granulocytes and macrophages via a distinct differentiation program that is tightly controlled by myeloid lineage-specific transcription factors. Mice with a null mutation of IFN Regulatory Factor 8 (IRF8) accumulate CD11b+Gr1+ myeloid cells that phenotypically and functionally resemble tumor-induced myeloid-derived suppressor cells (MDSCs), indicating an essential role of IRF8 in myeloid cell lineage differentiation. However, IRF8 is expressed in various types of immune cells and whether IRF8 functions intrinsically or extrinsically in regulation of myeloid cell lineage differentiation is not fully understood. Here we report an intriguing finding that although IRF8-deficient mice exhibit deregulated myeloid cell differentiation and resultant accumulation of CD11b+Gr1+ MDSCs, surprisingly, mice with IRF8 deficiency only in myeloid cells exhibit no abnormal myeloid cell lineage differentiation. Instead, mice with IRF8 deficiency only in T cells exhibited deregulated myeloid cell differentiation and MDSC accumulation. We further demonstrated that IRF8-deficient T cells exhibit elevated GM-CSF expression and secretion. Treatment of mice with GM-CSF increased MDSC accumulation, and adoptive transfer of IRF8-deficient T cells, but not GM-CSF-deficient T cells, increased MDSC accumulation in the recipient chimeric mice. Moreover, overexpression of IRF8 decreased GM-CSF expression in T cells. Our data determine that in addition to its intrinsic function as an apoptosis regulator in myeloid cells, IRF8 also acts extrinsically to represses GM-CSF expression in T cells to control myeloid cell lineage differentiation, revealing a novel mechanism that the adaptive immune component of the immune system regulates the innate immune cell myelopoiesis in vivo.
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常规树突状细胞在调节中性粒细胞骨髓释放和存活中的核心作用。
DOI：
10.4049/jimmunol.1300237
发表时间：
2014-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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影响因子：
2.3
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DOI：
10.4049/jimmunol.1001950
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Feng J;Wang H;Shin DM;Masiuk M;Qi CF;Morse HC 3rd
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3
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影响因子：
11.4
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