Askenase Michael H, Han Seong-Ji, Byrd Allyson L, Morais da Fonseca Denise, Bouladoux Nicolas, Wilhelm Christoph, Konkel Joanne E, Hand Timothy W, Lacerda-Queiroz Norinne, Su Xin-zhuan, Trinchieri Giorgio, Grainger John R, Belkaid Yasmine
Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
Program in Barrier Immunity and Repair, Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Immunity. 2015 Jun 16;42(6):1130-42. doi: 10.1016/j.immuni.2015.05.011. Epub 2015 Jun 9.
Tissue-infiltrating Ly6C(hi) monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. How and where this diversity of function is imposed remains poorly understood. Here we show that during acute gastrointestinal infection, priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Notably, natural killer (NK) cell-derived IFN-γ promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DCs) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals after tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function.
组织浸润性Ly6C（高表达）单核细胞在免疫中发挥多种作用，从病原体杀伤到免疫调节。这种功能多样性是如何以及在何处形成的仍知之甚少。在这里，我们表明在急性胃肠道感染期间，单核细胞的调节功能启动先于全身炎症，并且在骨髓逸出之前就已开始。值得注意的是，自然杀伤（NK）细胞衍生的IFN-γ在发育过程中促进单核细胞祖细胞中的调节程序。早期骨髓NK细胞的激活由黏膜相关淋巴组织（MALT）中Batf3依赖性树突状细胞（DCs）产生的全身白细胞介素-12（IL-12）控制。这项工作挑战了单核细胞功能主要由组织招募后的局部信号决定的范式，而是提出了一种分化的顺序模型，其中单核细胞在骨髓发育过程中被预先“教育”以促进其组织特异性功能。
