Maternal imprinting of autoreactivity in a murine model of systemic lupus erythematosus

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity Pub Date : 2025-07-28 DOI:10.1016/j.bbi.2025.07.025

Sofie V. Fonager , Gudrun Winther , Yamira C.L. Weber , Thomas R. Wittenborn , Kristian S. Kastberg , Ewa Terczyńska-Dyla , Lisbeth Jensen , Lisbeth A. Hansen , Michael C. Carroll , Yonglun Luo , Lin Lin , Søren E. Degn

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Abstract

Mammals confer passive immunity upon their offspring via transplacental IgG and postnatal transfer of milk IgA. Maternofetal microchimerism and the cytokine environment in utero may also influence the developing offspring. Normally protective maternal immune factors can adversely affect the offspring in the context of maternal autoimmune disease. Here, unexpectedly, we observed maternal imprinting of autoreactivity, presenting as spontaneous germinal centers (GCs) and endogenous autoantibody production, in a murine model of systemic lupus erythematosus (SLE). This prompted us to investigate how maternal autoimmune status can influence the offspring independently of genetic factors. Using embryo transfers to experimentally uncouple genetic from environmental maternal factors, we did not observe maternofetal microchimerism, but embryo transfer offspring of autoimmune dams received maternally derived IgG2A and anti-dsDNA antibodies. Moreover, they displayed increased formation of spontaneous GCs and elevated endogenous IgG2C autoantibody production. The neuroimmunological phenotype in offspring appeared unaffected. Taken together, our findings suggest maternal immune factors actively contribute to shape the susceptibility of offspring to autoimmune diseases independent of genetic factors.

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母体在系统性红斑狼疮小鼠模型中的自身反应性印记

哺乳动物通过胎盘IgG和产后乳汁IgA的传递将被动免疫赋予其后代。母胎微嵌合和子宫内的细胞因子环境也可能影响后代的发育。通常保护性的母体免疫因子在母体自身免疫性疾病的情况下会对后代产生不利影响。在系统性红斑狼疮（SLE）小鼠模型中，我们意外地观察到母体自身反应性印记，表现为自发生发中心（GCs）和内源性自身抗体的产生。这促使我们研究母亲自身免疫状态如何独立于遗传因素影响后代。通过胚胎移植，我们没有观察到母胎微嵌合现象，但自身免疫大坝的胚胎移植后代接受了母源性IgG2A和抗dsdna抗体。此外，他们表现出自发GCs的形成增加和内源性IgG2C自身抗体的产生增加。后代的神经免疫表型未受影响。综上所述，我们的研究结果表明，母亲的免疫因素积极地影响了后代对自身免疫性疾病的易感性，而不依赖于遗传因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain, Behavior, and Immunity 医学-免疫学

CiteScore

29.60

自引率

2.00%

发文量

290

审稿时长

28 days

期刊介绍： Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.