The immunometabolic function of VGLL3 and female-biased autoimmunity

The immunometabolic function of VGLL3 and female-biased autoimmunity

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DOI 10.1097/IN9.0000000000000041
刊名
IJ
年,卷(期) 2024, 6(2)
作者
作者单位

[Kennicott, Kameron;
Liang, Yun] Michigan State Univ, Dept Physiol, E Lansing, MI 48825 USA;
[Kennicott, Kameron;
Liang, Yun] Michigan State Univ, Dept Pharmacol & Toxicol, E Lansing, MI 48825 USA

摘要
Autoimmune diseases exhibit a pronounced yet unexplained prevalence among women. Vestigial-like family member 3 (VGLL3), a female-biased factor that promotes autoimmunity, has recently been discovered to assist cells in sensing and adapting to nutritional stress. This role of VGLL3 may confer a selective advantage during the evolution of placental mammals. However, the excessive activation of the VGLL3-mediated energy-sensing pathway can trigger inflammatory cell death and the exposure of self-antigens, leading to the onset of autoimmunity. These observations have raised the intriguing perspective that nutrient sensing serves as a double-edged sword in immune regulation. Mechanistically, VGLL3 intersects with Hippo signaling and activates multiple downstream, immune-associated genes that play roles in metabolic regulation. Understanding the multifaceted roles of VGLL3 in nutrient sensing and immune modulation provides insight into the fundamental question of sexual dimorphism in immunometabolism and sheds light on potential therapeutic targets for autoimmune diseases.
Abstract
Autoimmune diseases exhibit a pronounced yet unexplained prevalence among women. Vestigial-like family member 3 (VGLL3), a female-biased factor that promotes autoimmunity, has recently been discovered to assist cells in sensing and adapting to nutritional stress. This role of VGLL3 may confer a selective advantage during the evolution of placental mammals. However, the excessive activation of the VGLL3-mediated energy-sensing pathway can trigger inflammatory cell death and the exposure of self-antigens, leading to the onset of autoimmunity. These observations have raised the intriguing perspective that nutrient sensing serves as a double-edged sword in immune regulation. Mechanistically, VGLL3 intersects with Hippo signaling and activates multiple downstream, immune-associated genes that play roles in metabolic regulation. Understanding the multifaceted roles of VGLL3 in nutrient sensing and immune modulation provides insight into the fundamental question of sexual dimorphism in immunometabolism and sheds light on potential therapeutic targets for autoimmune diseases.
关键词
autoimmunity; immunometabolism; nutrient sensing; sexual dimorphism
KeyWord
autoimmunity; immunometabolism; nutrient sensing; sexual dimorphism
基金项目
页码 1-5
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Kennicott, Kameron; Liang, Yun. The immunometabolic function of VGLL3 and female-biased autoimmunity [J]. Immunometabolism. 2024; 6; (2). 1 - 5.

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