Interleukin-36γ-producing macrophages drive IL-17-mediated fibrosis.
Interleukin-36γ-producing macrophages drive IL-17-mediated fibrosis.
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DOI：
10.1126/sciimmunol.aax4783
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发表时间：
2019-10-11
影响因子：
24.8
通讯作者：
Elisseeff JH
中科院分区：
文献类型：
--
作者：
Sommerfeld SD;Cherry C;Schwab RM;Chung L;Maestas DR Jr;Laffont P;Stein JE;Tam A;Ganguly S;Housseau F;Taube JM;Pardoll DM;Cahan P;Elisseeff JH
生物材料诱导免疫应答和巨噬细胞动员，但体内功能性巨噬细胞亚群的鉴定和表型表征仍然有限。我们对从生物基质[膀胱基质（UBM）]或合成生物材料[聚己内酯（PCL）]中分选的巨噬细胞进行单细胞RNA测序分析。UBM的植入通过产生以T辅助细胞2（TH 2）/白细胞介素（IL）-4免疫特征为特征的组织环境来促进组织修复，而PCL诱导以TH 17/IL-17和纤维化为特征的标准异物反应。无偏聚类和伪时间分析揭示了不同的巨噬细胞亚群负责抗原呈递，化学吸引和吞噬作用，以及一个小的人口与树突状细胞和骨骼肌的表达谱后UBM植入。在PCL组织环境中，我们鉴定了表达TH 17相关分子的CD 9 hi +IL-36γ+巨噬细胞亚群。这些巨噬细胞在缺乏IL-17受体的小鼠中几乎不存在，表明它们可能参与IL-17依赖性免疫和自身免疫反应。小鼠和人体组织样本中独特的表型和功能性巨噬细胞亚群的鉴定和比较表明新分类的广泛相关性。这些不同的巨噬细胞亚群表现出先前未被识别的参与不同组织反应的髓样表型，并为组织修复和病理学中的潜在治疗调节提供了靶点。
Biomaterials induce an immune response and mobilization of macrophages, yet identification and phenotypic characterization of functional macrophage subsets in vivo remain limited. We performed single-cell RNA sequencing analysis on macrophages sorted from either a biologic matrix [urinary bladder matrix (UBM)] or synthetic biomaterial [polycaprolactone (PCL)]. Implantation of UBM promotes tissue repair through generation of a tissue environment characterized by a T helper 2 (TH2)/interleukin (IL)–4 immune profile, whereas PCL induces a standard foreign body response characterized by TH17/IL-17 and fibrosis. Unbiased clustering and pseudotime analysis revealed distinct macrophage subsets responsible for antigen presentation, chemoattraction, and phagocytosis, as well as a small population with expression profiles of both dendritic cells and skeletal muscle after UBM implantation. In the PCL tissue environment, we identified a CD9hi+IL-36γ+ macrophage subset that expressed TH17-associated molecules. These macrophages were virtually absent in mice lacking the IL-17 receptor, suggesting that they might be involved in IL-17–dependent immune and autoimmune responses. Identification and comparison of the unique phenotypical and functional macrophage subsets in mouse and human tissue samples suggest broad relevance of the new classification. These distinct macrophage subsets demonstrate previously unrecognized myeloid phenotypes involved in different tissue responses and provide targets for potential therapeutic modulation in tissue repair and pathology.
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影响因子：
16.6
作者：
MacParland SA;Liu JC;Ma XZ;Innes BT;Bartczak AM;Gage BK;Manuel J;Khuu N;Echeverri J;Linares I;Gupta R;Cheng ML;Liu LY;Camat D;Chung SW;Seliga RK;Shao Z;Lee E;Ogawa S;Ogawa M;Wilson MD;Fish JE;Selzner M;Ghanekar A;Grant D;Greig P;Sapisochin G;Selzner N;Winegarden N;Adeyi O;Keller G;Bader GD;McGilvray ID
通讯作者：
McGilvray ID
影响因子：
1.2
作者：
Khan, Muznah;Gasser, Stephan
通讯作者：
Gasser, Stephan
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
48
作者：
Kiselev, Vladimir Yu;Kirschner, Kristina;Hemberg, Martin
通讯作者：
Hemberg, Martin
影响因子：
2
作者：
Zambrano-Zaragoza JF;Romo-Martínez EJ;Durán-Avelar Mde J;García-Magallanes N;Vibanco-Pérez N
通讯作者：
Vibanco-Pérez N