» Articles » PMID: 39736777

PCSK9 in T-cell Function and the Immune Response

Overview
Journal Biomark Res
Publisher Biomed Central
Date 2024 Dec 31
PMID 39736777
Authors
Affiliations
Soon will be listed here.
Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) was first reported in 2003 and confirmed to be strongly associated with familial hypercholesterolemia. Small-molecule inhibitors targeting PCSK9 provide an effective and safe method for managing hypercholesterolemia and reducing the cardiovascular risk. In recent years, increasing evidence has indicated other important roles for PCSK9 in inflammation, tumors, and even immune regulation. PCSK9 might be an attractive regulator of T-cell activation and expansion. It might mediate inflammation and regulate other types of immune cells. In this review, we summarize the current advances in the field of PCSK9 and provide a narrative of the biological processes associated with PCSK9. The relationships between PCSK9 and different T cells were investigated in depth. Finally, the signaling pathways associated with PCSK9 and the immune response are also summarized in this review.

References
1.
Hampton E, Knuth M, Li J, Harris J, Lesley S, Spraggon G . The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain. Proc Natl Acad Sci U S A. 2007; 104(37):14604-9. PMC: 1976225. DOI: 10.1073/pnas.0703402104. View

2.
Ray K, Wright R, Kallend D, Koenig W, Leiter L, Raal F . Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020; 382(16):1507-1519. DOI: 10.1056/NEJMoa1912387. View

3.
Seidah N . The Elusive Inhibitory Function of the Acidic N-Terminal Segment of the Prodomain of PCSK9: The Plot Thickens. J Mol Biol. 2019; 431(5):904-907. DOI: 10.1016/j.jmb.2019.01.015. View

4.
Ding Q, Strong A, Patel K, Ng S, Gosis B, Regan S . Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res. 2014; 115(5):488-92. PMC: 4134749. DOI: 10.1161/CIRCRESAHA.115.304351. View

5.
Sengal A, Velazquez J, Hahne M, Burke T, Abhyankar H, Reyes R . Overcoming T-cell exhaustion in LCH: PD-1 blockade and targeted MAPK inhibition are synergistic in a mouse model of LCH. Blood. 2020; 137(13):1777-1791. PMC: 8020265. DOI: 10.1182/blood.2020005867. View