Compensatory dendritic cell development mediated bv BATF-IRF interactions

摘要

Kernneth Murphy及其同事研究了AP-1转录因子BATF在树状细胞分化(使CD8+T-细胞能够对细胞内病原体做出反应的一个过程)中所起作用，并为由相关家族成员所给予的分子补偿提供了证据。补偿是基于BATF亮氨酸“拉链”区域与干扰素调控因子IRF4和IRF8的相互作用进行的，以调节合作性基因活化。在另一项互补性研究中，Warren Leoilard及其同事提供的证据表明，IRF4通过与AP-1家族成员BATF和JUN的合作性结合相互作用调控CD4+ T-细胞分化和T_H 17功能。这些研究为操纵依赖于BAT-IRF4相互作用的关键免疫反应指出了潜在的新目标。%The API transcription factor Batf3 is required for homeostatic development of CD8α~+ classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Barf3-independent pathway in mice for CD8ot+ dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL) -12 and interferon-γ. This alternative pathway results from molecular compensation for Batf3 provided by the related AP1 factors Batf, which also functions in T and B cells, and Batf2 induced by cytokines in response to infection. Reciprocally, physiological compensation between Batf and Batf3 also occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF factors is based on the shared capacity of their leucine zipper domains to interact with non-API factors such as IRF4 and IRF8 to mediate cooperative gene activation. Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines.