Adaptive Immune Regulation of Mammary Postnatal Organogenesis.
Adaptive Immune Regulation of Mammary Postnatal Organogenesis.
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DOI：
10.1016/j.devcel.2015.07.015
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发表时间：
2015-09-14
影响因子：
11.8
通讯作者：
Werb Z
中科院分区：
文献类型：
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作者：
Plaks V;Boldajipour B;Linnemann JR;Nguyen NH;Kersten K;Wolf Y;Casbon AJ;Kong N;van den Bijgaart RJ;Sheppard D;Melton AC;Krummel MF;Werb Z
出生后的器官发生在免疫环境中，并受到正负调节因子之间相互作用的严格控制。先天免疫细胞在出生后组织重塑中具有有益的作用，但适应性免疫系统的作用目前尚未探索。在这里，我们表明，适应性免疫反应参与正常的出生后发育的非淋巴上皮组织。由于乳腺（MG）是出生后主要发育的唯一器官，我们利用它作为一个强大的系统来研究器官发生的适应性免疫调节。我们发现，乳腺抗原呈递细胞和产生干扰素-γ（IFNγ）的CD 4 + T辅助细胞1之间的抗原介导的相互作用作为负调节因子参与MG出生后器官发生，局部协调上皮重排。IFNγ然后影响管腔谱系分化。这种调节正常发育的适应性免疫反应的功能改变了研究出生后器官发生的参与者的范式，并为免疫监视和癌症转化提供了见解。
Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland (MG) is the only organ developing predominantly after birth, we utilized it as a powerful system to study adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ (IFNγ)-producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses regulating normal development changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation.