Monocyte Chemoattractant Protein-1 Contributes to Gut Homeostasis and Intestinal Inflammation by Composition of IL-10–Producing Regulatory Macrophage Subset
Monocyte Chemoattractant Protein-1 Contributes to Gut Homeostasis and Intestinal Inflammation by Composition of IL-10–Producing Regulatory Macrophage Subset
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DOI：
10.4049/jimmunol.0804012
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发表时间：
2010-03
期刊：
影响因子：
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通讯作者：
Y. Takada;T. Hisamatsu;N. Kamada;M. Kitazume;Haruki Honda;Yosuke Oshima;R. Saito;T. Takayama;
中科院分区：
文献类型：
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作者：
Y. Takada;T. Hisamatsu;N. Kamada;M. Kitazume;Haruki Honda;Yosuke Oshima;R. Saito;T. Takayama;
固有层巨噬细胞（LPM巨噬细胞）自发产生大量抗炎性IL-10，并在调节针对肠道细菌的免疫应答中发挥核心作用。MCP-1是一种趋化因子，在单核细胞和巨噬细胞向炎症组织的募集中起重要作用。我们证明，除了IL-10，LPM细胞产生大量的MCP-1，即使在稳定状态下。MCP-1缺乏导致LPM结肠炎细胞产生IL-10受损，并导致葡聚糖硫酸钠诱导的急性结肠炎加重。作为LPM β细胞产生IL-10受损的一种解释，我们发现LPM β细胞可以分为两个具有不同侧向散射特性的亚群，即LPM β 1（CD 11b +F4/80+ CD 11 c-SSCi）和LPM β 2（CD 11b +F4/80+ CD 11 c-SSCio）。与LPM 101不同，LPM 102亚群响应于MCP-1而迁移，并响应于共生细菌而产生更大量的IL-10。由于缺乏MCP-1依赖性LPM β 2群体，从MCP-1缺陷小鼠中分离的LPM β产生较少的IL-10。这种LPM大肠杆菌群体的不平衡组成可能与MCP-1缺陷小鼠对DSS诱导的结肠炎的易感性有关。我们的研究结果表明，内源性MCP-1有助于居民的LPM在肠道中的亚群的组成。此外，MCP-1依赖性LPM β 2亚群可能通过产生IL-10在维持稳态的肠道稳态和终止肠道过度炎症反应中发挥重要作用。
Lamina propria macrophages (LPMϕs) spontaneously produce large amounts of anti-inflammatory IL-10 and play a central role in regulation of immune responses against commensal bacteria. MCP-1 is a chemokine that plays an important role in recruitment of monocytes and macrophages to inflamed tissues. We demonstrated that, in addition to IL-10, LPMϕs produced large amounts of MCP-1, even in a steady state. MCP-1 deficiency caused impaired IL-10 production by LPMϕs and led to exacerbation of dextran sulfate sodium-induced acute colitis. As an explanation of this impaired IL-10 production by LPMϕs, we found that LPMϕs could be separated into two subsets with distinct side-scattered properties, namely LPMϕ1 (CD11b+F4/80+CD11c–SSChi) and LPMϕ2 (CD11b+F4/80+CD11c–SSClo). Unlike LPMϕ1, the LPMϕ2 subset migrated in response to MCP-1 and produced a larger amount of IL-10 in response to commensal bacteria. LPMϕs isolated from MCP-1–deficient mice produced less IL-10 as a consequence of the lack of the MCP-1–dependent LPMϕ2 population. This imbalanced composition in LPMϕ population may be involved in the susceptibility to DSS-induced colitis in MCP-1–deficient mice. Our results suggest that endogenous MCP-1 contributes to the composition of resident LPMϕ subsets in the intestine. Moreover, MCP-1–dependent LPMϕ2 subset may play an important role in maintenance of gut homeostasis in the steady state, and in the termination of excess inflammatory responses in the intestine, by producing IL-10.