Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that int...Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP- Jas an essential regulator of differentiation and function of alternatively activated macrophages.展开更多
基金We thank Tasuko Honjo for providing Rbpj^flox/flox mice, Keiko Ozato for providing Ifr8^-/- mice, and Karmen Au for technical assistance. LBI and BZ are supported by the grants from NIH. XH is supported by the National Basic Research Program （973 Program） （No. 2015CB943201）, National Natural Science Foundation of China Young Investigator Award 81422019, and funds from Peking-Tsin- ghua Center of Life Sciences.
文摘Development of alternatively activated （M2） macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP- Jas an essential regulator of differentiation and function of alternatively activated macrophages.
