巨噬细胞极化
巨噬细胞
炎症
M2巨噬细胞
粒细胞巨噬细胞集落刺激因子
免疫学
先天性淋巴细胞
结肠炎
炎症性肠病
生物
串扰
免疫
医学
细胞因子
免疫系统
病理
疾病
体外
物理
光学
生物化学
作者
Tomas Castro‐Dopico,Aaron Fleming,Thomas W. Dennison,John R. Ferdinand,Katherine Harcourt,Benjamin J Stewart,M Zaeem Cader,Zewen Kelvin Tuong,Chenzhi Jing,Laurence S.C. Lok,Rebeccah J. Mathews,Anaïs Portet,Arthur Kaser,Simon Clare,Menna R. Clatworthy
出处
期刊:Cell Reports
[Elsevier]
日期:2020-07-01
卷期号:32 (1): 107857-107857
被引量:82
标识
DOI:10.1016/j.celrep.2020.107857
摘要
Macrophages play a central role in intestinal immunity, but inappropriate macrophage activation is associated with inflammatory bowel disease (IBD). Here, we identify granulocyte-macrophage colony stimulating factor (GM-CSF) as a critical regulator of intestinal macrophage activation in patients with IBD and mice with dextran sodium sulfate (DSS)-induced colitis. We find that GM-CSF drives the maturation and polarization of inflammatory intestinal macrophages, promoting anti-microbial functions while suppressing wound-healing transcriptional programs. Group 3 innate lymphoid cells (ILC3s) are a major source of GM-CSF in intestinal inflammation, with a strong positive correlation observed between ILC or CSF2 transcripts and M1 macrophage signatures in IBD mucosal biopsies. Furthermore, GM-CSF-dependent macrophage polarization results in a positive feedback loop that augmented ILC3 activation and type 17 immunity. Together, our data reveal an important role for GM-CSF-mediated ILC-macrophage crosstalk in calibrating intestinal macrophage phenotype to enhance anti-bacterial responses, while inhibiting pro-repair functions associated with fibrosis and stricturing, with important clinical implications.
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