The Adaptor Protein CARD9 Protects against Colon Cancer by Restricting Mycobiota-Mediated Expansion of Myeloid-Derived Suppressor Cells.
The Adaptor Protein CARD9 Protects against Colon Cancer by Restricting Mycobiota-Mediated Expansion of Myeloid-Derived Suppressor Cells.
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接头蛋白 CARD9 通过限制分枝菌介导的骨髓来源抑制细胞的扩增来预防结肠癌
DOI：
10.1016/j.immuni.2018.08.018
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发表时间：
2018-09-18
期刊：
影响因子：
32.4
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Wang T;Fan C;Yao A;Xu X;Zheng G;You Y;Jiang C;Zhao X;Hou Y;Hung MC;Lin X
衔接蛋白CARD 9将表面受体对真菌的检测与NF-κB途径的激活联系起来。缺乏CARD 9的小鼠表现出生态失调，更容易患结肠炎。在这里，我们研究了Card 9缺陷在结肠炎相关结肠癌（CAC）发展中的影响。与WT小鼠相比，用AOM-DSS治疗Card 9 −/−小鼠导致肿瘤负荷增加，并导致骨髓源性抑制细胞（MDSC）在肿瘤组织中积累。Card 9 −/−巨噬细胞的杀真菌功能受损导致真菌负荷增加和肠道真菌生物群整体组成的变化，其中C.热带植物骨髓细胞与C. tropicalis具有MDSC特征和抑制功能。氟康唑治疗抑制了Card 9 −/−小鼠的CAC，并与MDSC蓄积减少相关。结肠癌患者肿瘤组织中MDSC的频率与真菌负荷呈正相关，这表明该调节轴与人类疾病相关。衔接蛋白CARD 9在抗真菌免疫中起着至关重要的作用，将表面受体对真菌的检测与NF-κB途径的激活联系起来。Wang等人表明，Card 9 −/−小鼠更容易患结肠炎相关癌症，并概述了真菌生态失调增加骨髓源性抑制细胞频率的机制，从而有助于肿瘤发生。
The adaptor protein CARD9 links detection of fungi by surface receptors to the activation of the NF-κB pathway. Mice deficient in CARD9 exhibit dysbiosis and are more susceptible to colitis. Here we examined the impact of Card9 deficiency in the development of colitis-associated colon cancer (CAC). Treatment of Card9−/−mice with AOM-DSS resulted in increased tumor loads as compared to WT mice and in the accumulation of myeloid-derived suppressor cells (MDSCs) in tumor tissue. The impaired fungicidal functions of Card9−/− macrophages led to increased fungal loads and variation in the overall composition of the intestinal mycobiota, with a notable increase in C. tropicalis. Bone marrow cells incubated with C. tropicalis exhibited MDSC features and suppressive functions. Fluconazole treatment suppressed CAC in Card9−/− mice and was associated with decreased MDSC accumulation. The frequency of MDSCs in tumor tissues of colon cancer patients correlated positively with fungal burden, pointing to the relevance of this regulatory axis in human disease. The adaptor protein CARD9 plays a crucial role in anti-fungal immunity, linking detection of fungi by surface receptors to the activation of the NF-κB pathway. Wang et al. show that Card9−/− mice are more susceptible to colitis-associated cancer and outline a mechanism whereby fungal dysbiosis increases the frequency of myeloid-derived suppressor cells, thus contributing to tumorigenesis.
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影响因子：
16.6
作者：
Arthur, Janelle C.;Gharaibeh, Raad Z.;Muehlbauer, Marcus;Perez-Chanona, Ernesto;Uronis, Joshua M.;McCafferty, Jonathan;Fodor, Anthony A.;Jobin, Christian
通讯作者：
Jobin, Christian
影响因子：
5.5
作者：
Bunt, Stephanie K.;Clements, Virginia K.;Ostrand-Rosenberg, Suzanne
通讯作者：
Ostrand-Rosenberg, Suzanne
影响因子：
29.4
作者：
Landers, CJ;Cohavy, O;Targan, SR
通讯作者：
Targan, SR
TLR4/MyD88 诱导的 CD11b+Gr-1 int F4/80+ 非迁移性骨髓细胞抑制肺部的 Th2 效应器功能。
影响因子：
8
作者：
Arora, M.;Poe, S. L.;Oriss, T. B.;Krishnamoorthy, N.;Yarlagadda, M.;Wenzel, S. E.;Billiar, T. R.;Ray, A.;Ray, P.
通讯作者：
Ray, P.
影响因子：
4.5
作者：
Beaudoin M;Goyette P;Boucher G;Lo KS;Rivas MA;Stevens C;Alikashani A;Ladouceur M;Ellinghaus D;Törkvist L;Goel G;Lagacé C;Annese V;Bitton A;Begun J;Brant SR;Bresso F;Cho JH;Duerr RH;Halfvarson J;McGovern DP;Radford-Smith G;Schreiber S;Schumm PL;Sharma Y;Silverberg MS;Weersma RK;Quebec IBD Genetics Consortium;NIDDK IBD Genetics Consortium;International IBD Genetics Consortium;D'Amato M;Vermeire S;Franke A;Lettre G;Xavier RJ;Daly MJ;Rioux JD
通讯作者：
Rioux JD