B Cell Activation and Plasma Cell Differentiation Are Promoted by IFN-λ in Systemic Lupus Erythematosus.
B Cell Activation and Plasma Cell Differentiation Are Promoted by IFN-λ in Systemic Lupus Erythematosus.
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DOI：
10.4049/jimmunol.2100339
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发表时间：
2021-12-01
期刊：
影响因子：
--
通讯作者：
Anolik JH
中科院分区：
文献类型：
--
作者：
Barnas JL;Albrecht J;Meednu N;Alzamareh DF;Baker C;McDavid A;Looney RJ;Anolik JH
I型干扰素（IFN）对病毒清除至关重要，但也有助于自身免疫性疾病的发病机制，如系统性红斑狼疮（SLE），通过异常的核酸感应途径导致自身抗体的产生。III型IFN （IFN-λ）现在被认为在病毒感染中具有非冗余的作用，但由于其受体主要在上皮中表达受限，因此很少有研究涉及IFN-λ对免疫细胞的影响。在这里，我们证明B细胞在狼疮患者中显示出突出的IFN基因表达谱。血清IFN-λ水平在SLE中升高，并与自身免疫浆细胞（PC）发展相关的B细胞亚群呈正相关，包括CD11c+ T-bet+ CD21- B细胞。虽然B细胞亚群表达所有IFN受体，但IFNLR1与CD11c+ CD21- B细胞扩增强烈相关，这表明IFN-λ可能是SLE IFN信号和B细胞异常的未被发现的驱动因素。我们发现，在BCR和TLR7/8刺激后，IFN-λ增强了人类B细胞中通常归因于I型IFN的基因转录，以及表达T-bet的B细胞的扩增。此外，IFN-λ促进tlr7 /8介导的质母细胞分化和增加IgM的产生。与其他B细胞亚群相比，CD11c+ B细胞表现出IFN-λ超反应信号，这表明IFN-λ通过这一假定的滤泡外途径加速了PC分化。总之，我们的数据支持III型IFN-λ作为细胞因子促进人类病毒和自身免疫性疾病的抗体分泌细胞池。
Type I interferon (IFN) is essential for viral clearance but also contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), via aberrant nucleic acid sensing pathways leading to autoantibody production. Type III IFN (IFN-λ) is now appreciated to have a non-redundant role in viral infection, but few studies have addressed the effects of IFN-λ on immune cells given the more restricted expression of its receptor primarily to the epithelium. Here, we demonstrate that B cells display a prominent IFN gene expression profile in lupus patients. Serum levels of IFN-λ are elevated in SLE and positively correlate with B cell subsets associated with autoimmune plasma cell (PC) development, including CD11c+ T-bet+ CD21- B cells. Although B cell subsets express all IFN receptors, IFNLR1 strongly correlates with the CD11c+ CD21- B cell expansion, suggesting that IFN-λ may be an unappreciated driver of the SLE IFN signature and B cell abnormalities. We show that IFN-λ potentiates gene transcription in human B cells typically attributed to type I IFN as well as expansion of T-bet expressing B cells after BCR and TLR7/8 stimulation. Further, IFN-λ promotes TLR7/8-mediated plasmablast differentiation and increased IgM production. CD11c+ B cells demonstrate IFN-λ hyper-responsive signaling compared to other B cell subsets suggesting that IFN-λ accelerates PC differentiation through this putative extra-follicular pathway. In summary, our data support type III IFN-λ as a cytokine promoting the antibody-secreting cell pool in human viral and autoimmune disease.
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影响因子：
4.9
作者：
Grammer AC;Lipsky PE
通讯作者：
Lipsky PE
影响因子：
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作者：
Hemann EA;Gale M Jr;Savan R
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DOI：
10.1016/s2213-2600(20)30566-x
发表时间：
2021-05
期刊：
The Lancet. Respiratory medicine
影响因子：
--
作者：
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影响因子：
20.3
作者：
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4.9
作者：
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通讯作者：
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