The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/-) mice.
The cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/-) mice.
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DOI：
10.1371/journal.pone.0187432
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Dimayuga PC
中科院分区：
文献类型：
--
作者：
Mihailovic PM;Lio WM;Yano J;Zhao X;Zhou J;Chyu KY;Shah PK;Cercek B;Dimayuga PC
自身免疫被认为是动脉粥样硬化中炎症的原因。抗微生物肽LL-37是凯萨林菌素蛋白前体hCAP 18的一个片段，先前被鉴定为银屑病中的自身抗原。考虑到银屑病和冠状动脉疾病之间的联系，在体外使用hCAP 18的小鼠同源物CRAMP的截短（t）形式对来自动脉粥样硬化倾向ApoE（-/-）小鼠的脾细胞测试自身抗原与动脉粥样硬化的生物学相关性。用tCRAMP刺激导致ApoE（-/-）小鼠中具有中枢记忆和效应记忆表型的CD 8 + T细胞增加，其通过用正常食物或高脂肪饮食喂养而差异活化。用不同剂量的缩短肽（Cramp）免疫ApoE（-/-）导致不同的结果，较低剂量减少动脉粥样硬化，而较高剂量加重疾病，动脉粥样硬化斑块的中性粒细胞浸润增加。低剂量Cramp免疫还导致脾CD 8 + T细胞脱粒增加和CD 11b + CD 11 c+常规树突状细胞（cDC）减少，而高剂量增加CD 11b + CD 11 c + cDC。我们的研究结果确定CRAMP，小鼠同源的hCAP-18，作为一个潜在的自身抗原参与免疫反应的动脉粥样硬化的ApoE（-/-）小鼠模型。
Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (t) form of the mouse homolog of hCAP18, CRAMP, on splenocytes from athero-prone ApoE(-/-) mice. Stimulation with tCRAMP resulted in increased CD8+ T cells with Central Memory and Effector Memory phenotypes in ApoE(-/-) mice, differentially activated by feeding with normal chow or high fat diet. Immunization of ApoE(-/-) with different doses of the shortened peptide (Cramp) resulted in differential outcomes with a lower dose reducing atherosclerosis whereas a higher dose exacerbating the disease with increased neutrophil infiltration of the atherosclerotic plaques. Low dose Cramp immunization also resulted in increased splenic CD8+ T cell degranulation and reduced CD11b+CD11c+ conventional dendritic cells (cDCs), whereas high dose increased CD11b+CD11c+ cDCs. Our results identified CRAMP, the mouse homolog of hCAP-18, as a potential self-antigen involved in the immune response to atherosclerosis in the ApoE(-/-) mouse model.
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影响因子：
120.7
作者：
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通讯作者：
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DOI：
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发表时间：
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