Anti-galectin-3 antibodies induce skin vascular inflammation via promoting local production of IL-1β in systemic lupus erythematosus.
Anti-galectin-3 antibodies induce skin vascular inflammation via promoting local production of IL-1β in systemic lupus erythematosus.
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抗半乳糖凝集素 3 抗体通过促进系统性红斑狼疮局部产生 IL-1β 诱导皮肤血管炎症。
DOI：
10.1016/j.intimp.2022.109197
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发表时间：
2022-09
影响因子：
5.6
通讯作者：
Liangchun Wang
中科院分区：
文献类型：
--
作者：
Zhenrui Shi;Yu-ping Zhang;Dan Hong;Xiaonan Qiu;Lin Zheng;Lijuan Bian;Fengqiu Hu;Liuyu Chen;Hui Xiong;Qiongqiong Yang;Shanping Jiang;Guozhen Tan;Liangchun Wang
系统性红斑狼疮（SLE）患者的所有器官和组织均可发生血管炎症，其中皮肤最为常见。我们之前的研究发现抗半乳糖凝集素 3 (Gal3) 抗体 (Abs) 是狼疮皮肤血管病变的重要介质。在此，我们发现抗 Gal3 Abs 会失调血管内皮细胞的功能，导致 IL-1β 转录水平升高，并增加成熟 IL-1β 的表达。内皮细胞分泌的IL-1β的产生增强依赖于NLRP3炎性体。小鼠皮内注射抗 Gal3 Ab 会引起局部炎症，伴有 T 细胞和中性粒细胞血管周围浸润，而 IL-1β 阻断可抑制这种炎症。通过 Gal3 抗原免疫诱导循环中的抗 Gal3 抗体不仅导致皮肤的组织病理学变化，包括局灶性角质形成细胞空泡化和血管增厚，而且还导致涉及自身抗体产生和肾脏损伤的全身性自身免疫表型。有趣的是，IL-1β 的局部过度表达主要与小鼠的皮肤损伤有关，但与其他内脏器官无关。最后，我们发现 SLE 患者和健康供体之间的 IL-1β 血清水平相当。而与健康正常皮肤相比，狼疮皮损血管周围炎症局部区域IL-1β的表达较丰富。结果强烈表明，IL-1β 在介导抗 Gal3 Ab 诱导的皮肤血管炎症中发挥重要作用，并提出了使用 IL-1β 阻断疗法治疗狼疮皮肤损伤的前景。
Vascular inflammation could occur in all organs and tissues in patients with systematic lupus erythematosus (SLE), of which skin is the most frequent one. Our previous research identified anti-galectin-3 (Gal3) antibodies (Abs) as an important mediator of lupus cutaneous vasculopathy. Herein, we showed that anti-Gal3 Abs dysregulated the function of vascular endothelial cells with higher transcript levels of IL-1β and increased expression of mature IL-1β. The enhanced production of IL-1β secreted by endothelial cells was dependent on NLRP3 inflammasome. Intradermal injection of anti-Gal3 Abs in mice induced local inflammation with perivascular infiltration of T cells and neutrophils, which was inhibited by IL-1β blockade. Induction of anti-Gal3 Abs in circulation by immunization of Gal3 antigen not only led to histopathologic changes in the skin, including focal keratinocytes vacuolization and thickening of blood vessels, but also a systemic autoimmune phenotype that involves autoantibody production and kidney damage. Intriguingly, local overexpression of IL-1β was primarily associated with skin lesions but not with other internal organs in mice. Finally, we showed that the serum levels of IL-1β were comparable between SLE patients and healthy donors. Whilst the expression of IL-1β was enriched in local area with perivascular inflammation in lupus skin lesion compared to healthy normal skin. The results strongly suggest that IL-1β plays an important role in mediating anti-Gal3 Ab-induced skin vascular inflammation and raised the prospect for using IL-1β blocking therapies to treat lupus cutaneous damage.
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影响因子：
3.8
作者：
Nielsen CT;Østergaard O;Rasmussen NS;Jacobsen S;Heegaard NHH
通讯作者：
Heegaard NHH
糖原合酶激酶 3 beta 通过激活狼疮易感小鼠的 NLRP3 炎症小体促进肾损伤
DOI：
10.1002/art.38993
发表时间：
2015-04
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Zhao J;Wang H;Huang Y;Zhang H;Wang S;Gaskin F;Yang N;Fu SM
通讯作者：
Fu SM
影响因子：
9.5
作者：
Zhang C
通讯作者：
Zhang C
DOI：
10.1016/s0140-6736(01)05732-4
发表时间：
2001-08
期刊：
The Lancet
影响因子：
--
作者：
P. Stratta;C. Canavese;S. Santi;G. Ciccone;S. Rosso
通讯作者：
P. Stratta;C. Canavese;S. Santi;G. Ciccone;S. Rosso
影响因子：
1.6
作者：
Brugos, B.;Vincze, Z.;Zeher, M.
通讯作者：
Zeher, M.