Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.
Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes.
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DOI：
10.3389/fimmu.2021.661290
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发表时间：
2021
影响因子：
7.3
通讯作者：
Hammer GE
中科院分区：
文献类型：
--
作者：
Huang HI;Jewell ML;Youssef N;Huang MN;Hauser ER;Fee BE;Rudemiller NP;Privratsky JR;Zhang JJ;Reyes EY;Wang D;Taylor GA;Gunn MD;Ko DC;Cook DN;Chandramohan V;Crowley SD;Hammer GE
肠道免疫是由多种细胞亚群组成的特殊的单核吞噬细胞群协调的。虽然构成单核吞噬细胞网络的细胞亚群在小肠和大肠中被认为是相似的，但这些器官具有不同的解剖结构、微生物组成和免疫需求。这些区别是否需要器官特异性的单核吞噬细胞群在免疫中具有专门的器官特异性作用尚不清楚。在这里，我们实施了一种新的策略来亚群小鼠肠道单核吞噬细胞，并确定了两个新的亚群，它们是结肠特异性的：巨噬细胞亚群和th17诱导的树突状细胞（DC）亚群。结肠特异性dc和巨噬细胞共同表达CD24和CD14，令人惊讶的是，两者都依赖于转录因子IRF4。新型irf4依赖性CD14+CD24+巨噬细胞与传统巨噬细胞明显不同，不能表达CX3CR1、CD64和CD88等经典标志物，并且令人惊讶地表达少量IL-10，而其他所有肠道巨噬细胞都能强烈表达IL-10。我们进一步发现结肠特异性CD14+CD24+单核吞噬细胞对结肠Th17免疫至关重要，并提供了明确的证据，证明结肠和小肠对Th17免疫有不同的抗原提呈细胞需求。我们的研究结果揭示了肠道内单核吞噬细胞的器官特异性多样性和Th17免疫的器官特异性需求。
Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large intestine, these organs have distinct anatomy, microbial composition, and immunological demands. Whether these distinctions demand organ-specific mononuclear phagocyte populations with dedicated organ-specific roles in immunity are unknown. Here we implement a new strategy to subset murine intestinal mononuclear phagocytes and identify two novel subsets which are colon-specific: a macrophage subset and a Th17-inducing dendritic cell (DC) subset. Colon-specific DCs and macrophages co-expressed CD24 and CD14, and surprisingly, both were dependent on the transcription factor IRF4. Novel IRF4-dependent CD14+CD24+ macrophages were markedly distinct from conventional macrophages and failed to express classical markers including CX3CR1, CD64 and CD88, and surprisingly expressed little IL-10, which was otherwise robustly expressed by all other intestinal macrophages. We further found that colon-specific CD14+CD24+ mononuclear phagocytes were essential for Th17 immunity in the colon, and provide definitive evidence that colon and small intestine have distinct antigen presenting cell requirements for Th17 immunity. Our findings reveal unappreciated organ-specific diversity of intestine-resident mononuclear phagocytes and organ-specific requirements for Th17 immunity.
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DOI：
10.1084/jem.20170057
发表时间：
2018-02-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bujko A;Atlasy N;Landsverk OJB;Richter L;Yaqub S;Horneland R;Øyen O;Aandahl EM;Aabakken L;Stunnenberg HG;Bækkevold ES;Jahnsen FL
通讯作者：
Jahnsen FL
影响因子：
30.3
作者：
Johansson ME;Jakobsson HE;Holmén-Larsson J;Schütte A;Ermund A;Rodríguez-Piñeiro AM;Arike L;Wising C;Svensson F;Bäckhed F;Hansson GC
通讯作者：
Hansson GC
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
7.7
作者：
Gross-Vered, Mor;Trzebanski, Sebastien;Jung, Steffen
通讯作者：
Jung, Steffen
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR