Increased cAMP-PKA signaling pathway activation is involved in up-regulation of CTLA-4 expression in CD4+T cells in acute SIVmac239-infected Chinese rhesus macaques

	Increased cAMP-PKA signaling pathway activation is involved in up-regulation of CTLA-4 expression in CD4+T cells in acute SIVmac239-infected Chinese rhesus macaques
	Tian, RR; Liu, BB; Zhao, ML; Cai, YJ; Zheng, YT
	2024
发表期刊	VIRUS RESEARCH
ISSN	0168-1702
卷号	34
摘要	Human immunodeficiency virus-1 (HIV-1) infection can cause chronic activation, exhaustion, and anergy of the immune system. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint molecule, which plays an important role in immune homeostasis and disease. CTLA-4 expression is elevated in HIV-1infected patients and is associated with disease progression. However, the mechanism controlling expression of CTLA-4 in HIV-1 infection is poorly characterized. In this study, we used a SIV-infected Chinese rhesus macaque (ChRM) model to explore CTLA-4 expression in SIV infection. Results showed that SIV infection significantly increased CTLA-4 expression in all T cell subsets, especially central memory T cells. CTLA-4+CD4+ T cell frequency was significantly associated with disease progression markers. Activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway regulated CTLA-4 expression in CD4+T cells, as confirmed by stimulation with dibutyryl cyclic adenosine monophosphate, forskolin, and 3-isobutyl-1-methylxanthine, and inhibition with H-89 ex vivo. Simultaneously, cAMP concentration in PBMCs and PKA activity in both PBMCs and CD4+ T cells were increased in acute SIV-infected ChRMs, accompanied by an increase in adenylate cyclase 6 expression and a decrease in cAMP-phosphodiesterase 3A (PDE3A), PDE4B, and PDE5A expression in PBMCs. In addition, selective inhibition of PDE4B and PDE5A activity enhanced CTLA-4 expression in CD4+ T cells. These results suggest that SIV infection alters cAMP metabolism and increases cAMP-PKA signaling pathway activation, which up-regulates the expression of CTLA-4 in acute SIVmac239-infected ChRMs. Thus, regulation of the cAMP-PKA signaling pathway may be a potential strategy for the restoration of T cell function and therapy for AIDS.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14202
专题	科研部门_分子免疫药理学（郑永唐）
推荐引用方式 GB/T 7714	Tian, RR,Liu, BB,Zhao, ML,et al. Increased cAMP-PKA signaling pathway activation is involved in up-regulation of CTLA-4 expression in CD4+T cells in acute SIVmac239-infected Chinese rhesus macaques[J]. VIRUS RESEARCH,2024,34.
APA	Tian, RR,Liu, BB,Zhao, ML,Cai, YJ,&Zheng, YT.(2024).Increased cAMP-PKA signaling pathway activation is involved in up-regulation of CTLA-4 expression in CD4+T cells in acute SIVmac239-infected Chinese rhesus macaques.VIRUS RESEARCH,34.
MLA	Tian, RR,et al."Increased cAMP-PKA signaling pathway activation is involved in up-regulation of CTLA-4 expression in CD4+T cells in acute SIVmac239-infected Chinese rhesus macaques".VIRUS RESEARCH 34(2024).

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