Immune chromatin reader SP140 regulates microbiota and risk for inflammatory bowel disease.
Immune chromatin reader SP140 regulates microbiota and risk for inflammatory bowel disease.
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DOI：
10.1016/j.chom.2022.08.018
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发表时间：
2022-10-12
影响因子：
30.3
通讯作者：
Jeffrey, Kate L.
中科院分区：
文献类型：
--
作者：
Fraschilla, Isabella;Amatullah, Hajera;Rahman, Raza-Ur;Jeffrey, Kate L.
炎症性肠病（IBD）是由宿主遗传和环境因素驱动的，包括共生微生物。斑点蛋白140 （SP140）是一种免疫限制性染色质“解读器”，与克罗恩病（CD）、多发性硬化症（MS）和慢性淋巴细胞白血病（CLL）相关。然而，SP140的致病机制尚不明确。在这里，我们确定了SP140在调节吞噬防御反应以防止炎症细菌扩张中的免疫内在作用。由于造血Sp140缺乏导致微生物群改变的小鼠表现出严重的结肠炎，这种结肠炎在与抗生素共同居住和改善后可传播。SP140的缺失导致变形菌的大量繁殖，包括携带cd相关的SP140功能缺失变体的SP140 - / -小鼠中的幽门螺杆菌和人类中的肠杆菌科。患有SP140功能丧失变异的患者和SP140 - / -小鼠的吞噬细胞表现出控制病原体所需的抗菌防御程序的改变。因此，该表观遗传解读器内的突变可能构成由微生物群引起的人类疾病的易感事件。
Inflammatory bowel disease (IBD) is driven by host genetics and environmental factors, including commensal microorganisms. Speckled Protein 140 (SP140) is an immune-restricted chromatin ‘reader’ that is associated with Crohn’s disease (CD), multiple sclerosis (MS) and chronic lymphocytic leukemia (CLL). Yet, the disease-causing mechanisms of SP140 remain undefined. Here we identify an immune-intrinsic role for SP140 in regulating phagocytic defense responses to prevent the expansion of inflammatory bacteria. Mice harboring altered microbiota due to hematopoietic Sp140 deficiency exhibited severe colitis that was transmissible upon co-housing and ameliorated with antibiotics. Loss of SP140 results in blooms of Proteobacteria, including Helicobacter in Sp140−/− mice and Enterobacteriaceae in humans bearing the CD-associated SP140 loss-of-function variant. Phagocytes from patients with the SP140 loss-of-function variant and Sp140−/− mice exhibited altered antimicrobial defense programs required for control of pathobionts. Thus, mutations within this epigenetic reader may constitute a predisposing event in human diseases provoked by microbiota.
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影响因子：
24.8
作者：
Adiliaghdam, Fatemeh;Amatullah, Hajera;Digumarthi, Sreehaas;Saunders, Tahnee L.;Rahman, Raza-Ur;Wong, Lai Ping;Sadreyev, Ruslan;Droit, Lindsay;Paquette, Jean;Goyette, Philippe;Rioux, John D.;Hodin, Richard;Mihindukulasuriya, Kathie A.;Handley, Scott A.;Jeffrey, Kate L.
通讯作者：
Jeffrey, Kate L.
影响因子：
32.4
作者：
Britton, Graham J.;Contijoch, Eduardo J.;Faith, Jeremiah J.
通讯作者：
Faith, Jeremiah J.
影响因子：
30.5
作者：
通讯作者：
--
DOI：
10.1038/89675
发表时间：
2001-07-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Bottomley, MJ;Collard, MW;Sattler, M
通讯作者：
Sattler, M
影响因子：
3.1
作者：
Cahill, RJ;Foltz, CJ;Schauer, DB
通讯作者：
Schauer, DB