Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus.
Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus.
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DOI：
10.3390/ijms22031347
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发表时间：
2021-01-29
影响因子：
5.6
通讯作者：
Chevalier N
中科院分区：
文献类型：
--
作者：
Amend A;Wickli N;Schäfer AL;Sprenger DTL;Manz RA;Voll RE;Chevalier N
作为一种关键的抗炎细胞因子，IL-10在预防炎症性疾病和自身免疫性疾病中起着至关重要的作用。然而，在人类和小鼠狼疮中，它的作用仍然存在争议。我们的目的是了解IL-10对狼疮不同免疫功能的调节和免疫作用。在体外和体内对易患狼疮的NZB/W F1小鼠进行了这方面的探索，以了解IL-10对个体免疫细胞以及体内复杂环境的影响。我们发现，随着狼疮的进展，IL-10的多效性表达显著增加，而IL-10受体(IL-10R)水平保持相对稳定。体外实验显示了IL-10的促炎和抗炎作用。特别是，IL-10减少了促炎细胞因子，减缓了B细胞的增殖，从而触发了浆细胞的分化。ICOS、IL-21和cMAF的频繁共表达表明，产生IL-10的CD4T细胞在这方面是重要的B细胞助手。IL-10的体内外效应并不完全一致。体内IL-10R阻断可轻微加速狼疮临床表现和免疫功能紊乱。综上所述，我们在体外和体内并列比较IL-10对免疫的不同方面的影响，表明IL-10具有双重作用。我们的结果进一步表明，总体结果可能取决于不同因素的相互作用，如靶细胞、炎症和刺激微环境、疾病模式和状态。对这些影响的全面了解对于利用IL-10作为治疗靶点非常重要。
As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.
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影响因子：
4.9
作者：
Aringer M;Smolen JS
通讯作者：
Smolen JS
影响因子：
10.1
作者：
Dennis KL;Saadalla A;Blatner NR;Wang S;Venkateswaran V;Gounari F;Cheroutre H;Weaver CT;Roers A;Egilmez NK;Khazaie K
通讯作者：
Khazaie K
影响因子：
20.3
作者：
Fornek, JL;Tygrett, LT;Kansas, GS
通讯作者：
Kansas, GS
影响因子：
5
作者：
Blenman, Kim R. M.;Duan, Byian;Morel, Laurence
通讯作者：
Morel, Laurence
影响因子：
13.3
作者：
Chevalier, Nina;Macia, Laurence;Mackay, Charles R.
通讯作者：
Mackay, Charles R.