Cherfils-Vicini Julien, Vingert Benoit, Varin Audrey, Tartour Eric, Fridman Wolf-Herman, Sautès-Fridman Catherine, Régnier Catherine H, Cremer Isabelle
Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche des Cordeliers, Université Pierre et Marie Curie, Paris, France.
Immunology. 2008 Aug;124(4):562-74. doi: 10.1111/j.1365-2567.2008.02810.x. Epub 2008 Feb 18.
Tumour necrosis factor receptor associated factor 4 (TRAF4) is a member of the TRAF family of proteins which are cytoplasmic adaptor molecules strongly implicated in multiple immune functions. A previous investigation of TRAF4 biological functions by gene targeting in mice has shown a role for TRAF4 in embryonic development and neurulation in vivo. However, unlike other TRAF family members, the role of TRAF4 in the immune system is still unknown. To address this question, we performed an extensive characterization of the immune development and immune functions of TRAF4-deficient mice. Our analyses did not reveal any defects in development of T and B lymphocytes, granulocytes, macrophages and dendritic cells, and no defects in reactive oxygen species production and phagocytosis by neutrophils. Cellular and humoral responses against T-cell-dependent antigens were normal, as was dendritic cell maturation in response to microbial components and antigen uptake by dendritic cells. However, we demonstrated that dendritic cells from TRAF4-deficient mice exhibited reduced migration both in transwell experiments and in vivo. These results suggest that TRAF4 is not strictly required for immune development and functions but could participate in immune functions by facilitating immune cell migration.
肿瘤坏死因子受体相关因子4（TRAF4）是TRAF蛋白家族的成员，该家族蛋白是细胞质衔接分子，与多种免疫功能密切相关。先前通过基因敲除小鼠对TRAF4生物学功能进行的研究表明，TRAF4在体内胚胎发育和神经管形成中发挥作用。然而，与其他TRAF家族成员不同，TRAF4在免疫系统中的作用仍不清楚。为了解决这个问题，我们对TRAF4缺陷小鼠的免疫发育和免疫功能进行了广泛的表征。我们的分析未发现T和B淋巴细胞、粒细胞、巨噬细胞和树突状细胞发育存在任何缺陷，中性粒细胞产生活性氧和吞噬作用也无缺陷。针对T细胞依赖性抗原的细胞和体液反应正常，树突状细胞对微生物成分的反应成熟以及树突状细胞摄取抗原也正常。然而，我们证明，在Transwell实验和体内实验中，来自TRAF4缺陷小鼠的树突状细胞迁移均减少。这些结果表明，TRAF4并非免疫发育和功能所必需，但可能通过促进免疫细胞迁移参与免疫功能。
