The role of autoantibodies in bridging obesity, aging, and immunosenescence DOI Creative Commons
Taylor R. Valentino, Nan Chen, Priya Makhijani

et al.

Immunity & Ageing, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 30, 2024

Abstract Antibodies are essential to immune homeostasis due their roles in neutralizing pathogenic agents. However, failures central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance generate autoantibodies mistakenly target self-antigens, leading inflammation autoimmune diseases. While well-studied some communicable diseases, chronic conditions, such as obesity aging, less understood. Obesity aging share similar aspects of dysfunction, diminished humoral responses heightened inflammation, which disrupt tolerance foster autoantigen production, thus giving rise autoantibodies. In return, these events may also contribute the pathophysiology associated disorders linked development immunosenescence, an age-related decline function heightens vulnerability infections, loss self-tolerance. Furthermore, cumulative exposure antigens cellular debris during perpetuates pro-inflammatory pathways, linking immunosenescence with other hallmarks, proteostasis mitochondrial dysfunction. This review examines mechanisms driving autoantibody generation discusses key putative antigenic targets across conditions. We explore therapeutic potential emerging approaches, CAR-T/CAAR-T therapies, vaccines, BiTEs, tackle autoimmune-related conditions obesity.

Language: Английский

Laminaran potentiates cGAS-STING signaling to enhance antiviral responses DOI
Lingxiao Xu, Jiao Lyu, Zuo-Cheng Qiu

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 147, P. 114014 - 114014

Published: Jan. 9, 2025

Language: Английский

Citations

1
Cordycepin ameliorates autoimmunity by promoting STING degradation via autophagy pathway DOI Open Access
Deok‐Hwan Yang, Nana Peng,

Hongqian Zhang

et al.

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 15, 2024

Stimulator of interferon response cGAMP interactor 1 (STING), a central hub protein cyclic GMP-AMP synthase (cGAS)-STING signalling pathway, has crucial role in regulating type I interferons (IFNs) production and response. Recent studies indicate that excessive activation STING is strongly associated with autoimmune diseases, including systemic lupus erythematosus (SLE). Searching immunomodulators negatively regulate might greatly contribute to the suppression autoimmunity.

Language: Английский

Citations

3
SESN1 negatively regulates STING1 to maintain innate immune homeostasis DOI
Lingxiao Xu,

Hongqian Zhang,

Zuo-Cheng Qiu

et al.

Autophagy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 18

Published: Feb. 13, 2025

STING1 is a central hub protein of CGAS-STING1 signaling which important axis to sense DNA for the host against pathogens infection through regulating type I interferon (IFN-I) production. However, excessive activation-induced overproduced IFN-I triggers tissue damage and autoimmune disorders. Thus, activity must be precisely regulated immune homeostasis. Here, we discovered SESN1 (sestrin 1) as an essential negative regulator maintain Upon herpes simplex virus-1 (HSV-1) infection, expression was downregulated, enhanced potentiality virus defense host. Consistently, SESN1-deficient mice exhibited stronger ability HSV-1 compared wild-type littermates. Additionally, found decreased in systemic lupus erythematosus (SLE) patients trex1 KO mouse model disease. Intriguingly, replenishment effectively impressed production responses PBMCs human SLE specimens both vitro vivo. Mechanistically, targeted promoted autophagic degradation by facilitating interaction SQSTM1/p62 STING1. Together, our study uncovers crucial role homeostasis balance anti-virus autoimmunity might potential therapeutic target infectious diseases.Abbreviations: BMDMs: bone marrow-derived macrophages; cGAMP: cyclic GMP-AMP; CGAS: GMP-AMP synthase; HTDNA: herring testes DNA; IFNA4: alpha 4; IFNB: beta; IRF3: regulatory factor 3; ISD: stimulatory ISGs: IFN-stimulated genes; PBMCs: peripheral blood mononuclear cells; RSAD2: radical S-adenosyl methionine domain containing 2; SLE: erythematosus; STING1: stimulator response cGAMP interactor 1; TBK1: TANK binding kinase 1.

Language: Английский

Citations

0
The role of autoantibodies in bridging obesity, aging, and immunosenescence DOI Creative Commons
Taylor R. Valentino, Nan Chen, Priya Makhijani

et al.

Immunity & Ageing, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 30, 2024

Abstract Antibodies are essential to immune homeostasis due their roles in neutralizing pathogenic agents. However, failures central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance generate autoantibodies mistakenly target self-antigens, leading inflammation autoimmune diseases. While well-studied some communicable diseases, chronic conditions, such as obesity aging, less understood. Obesity aging share similar aspects of dysfunction, diminished humoral responses heightened inflammation, which disrupt tolerance foster autoantigen production, thus giving rise autoantibodies. In return, these events may also contribute the pathophysiology associated disorders linked development immunosenescence, an age-related decline function heightens vulnerability infections, loss self-tolerance. Furthermore, cumulative exposure antigens cellular debris during perpetuates pro-inflammatory pathways, linking immunosenescence with other hallmarks, proteostasis mitochondrial dysfunction. This review examines mechanisms driving autoantibody generation discusses key putative antigenic targets across conditions. We explore therapeutic potential emerging approaches, CAR-T/CAAR-T therapies, vaccines, BiTEs, tackle autoimmune-related conditions obesity.

Language: Английский

Citations

2