Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection

作者：Askenase Michael H; Han Seong Ji; Byrd Allyson L; da Fonseca Denise Morais; Bouladoux Nicolas; Wilhelm Christoph; Konkel Joanne E; Hand Timothy W; Lacerda Queiroz Norinne; Su Xin zhuan; Trinchieri Giorgio; Grainger John R^*; Belkaid Yasmine

来源：Immunity, 2015, 42(6): 1130-1142.

DOI：10.1016/j.immuni.2015.05.011

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-gamma 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.

• 出版日期2015-6-16