“…Therefore, inhibition of CARD9 signaling has been considered as a potential therapeutic strategy to the prevention and treatment of CVDs ( 4 ). Indeed, CARD9 deletion has been shown to prevent Coxsackievirus B3 (CVB3)-induced acute myocarditis ( 151 ), Candida albicans water-soluble extract (CAWS)-induced vasculitis ( 152 ), neointima formation of grafted veins ( 153 ), as well as TAC- or Angiotensin II (Ang II)-induced cardiac dysfunction, fibrosis, and hypertrophy ( 85 , 154 ), through attenuation of NF-κB, JNK and p38 MAPKs pathway, and production of various cytokines, such as IL-6, IL-1β, TNF-α, IL-17A, TGF-β, and IFN-γ. However, deletion of hematopoietic CARD9 shows no protective effects on atherosclerosis, probably because of no significant reduction of cytokines secretion (IL-6 and TNF-α) or mRNA expressions (IL-1β, IL-10, TNF-α, and MCP-1) ( 149 , 155 ).…”
Caspase-recruitment domain 9 (CARD9) protein is expressed in many cells especially in immune cells, and is critically involved in the function of the innate and adaptive immune systems through extensive interactions between CARD9 and other signaling molecules including NF-κB and MAPK. CARD9-mediated signaling plays a central role in regulating inflammatory responses and oxidative stress through the productions of important cytokines and chemokines. Abnormalities of CARD9 and CARD9 signaling or CARD9 mutations or polymorphism are associated with a variety of pathological conditions including infections, inflammation, and autoimmune disorders. This review focuses on the function of CARD9 and CARD9-mediated signaling pathways, as well as interactions with other important signaling molecules in different cell types and the relations to specific disease conditions including inflammatory diseases, infections, tumorigenesis, and cardiovascular pathologies.
“…Therefore, inhibition of CARD9 signaling has been considered as a potential therapeutic strategy to the prevention and treatment of CVDs ( 4 ). Indeed, CARD9 deletion has been shown to prevent Coxsackievirus B3 (CVB3)-induced acute myocarditis ( 151 ), Candida albicans water-soluble extract (CAWS)-induced vasculitis ( 152 ), neointima formation of grafted veins ( 153 ), as well as TAC- or Angiotensin II (Ang II)-induced cardiac dysfunction, fibrosis, and hypertrophy ( 85 , 154 ), through attenuation of NF-κB, JNK and p38 MAPKs pathway, and production of various cytokines, such as IL-6, IL-1β, TNF-α, IL-17A, TGF-β, and IFN-γ. However, deletion of hematopoietic CARD9 shows no protective effects on atherosclerosis, probably because of no significant reduction of cytokines secretion (IL-6 and TNF-α) or mRNA expressions (IL-1β, IL-10, TNF-α, and MCP-1) ( 149 , 155 ).…”
Caspase-recruitment domain 9 (CARD9) protein is expressed in many cells especially in immune cells, and is critically involved in the function of the innate and adaptive immune systems through extensive interactions between CARD9 and other signaling molecules including NF-κB and MAPK. CARD9-mediated signaling plays a central role in regulating inflammatory responses and oxidative stress through the productions of important cytokines and chemokines. Abnormalities of CARD9 and CARD9 signaling or CARD9 mutations or polymorphism are associated with a variety of pathological conditions including infections, inflammation, and autoimmune disorders. This review focuses on the function of CARD9 and CARD9-mediated signaling pathways, as well as interactions with other important signaling molecules in different cell types and the relations to specific disease conditions including inflammatory diseases, infections, tumorigenesis, and cardiovascular pathologies.
“…Moreover, they still confirmed that CARD9 deficiency did not affect the initiation of CD8 + T cell response. In a Coxsackievirus B3 (CVB3)-induced viral myocarditis mouse model, CARD9 deletion downregulated the mRNA and protein expression of TGF-β, IL-17A, and BCL-10, thereby ameliorating the CARD9-involved potent inflammation response (Sun et al, 2020 ). Based on these, a conflicting effect of CARD9 in viral infection is unfolding before our eyes.…”
Microbial infection, caused by fungi, bacteria, viruses, and parasites, significantly contributes to the global death burden and health costs. The innate and adaptive immune systems orchestrate a multifaceted signaling response to invading pathogens as the human antimicrobial system. In this process, caspase recruitment domain-containing protein 9 (CARD9) emerges as a critical intermediary adaptor molecule to participate in regulating a series of antimicrobial immune reactions. Previous publications have confirmed that CARD9 plays a crucial role in fungal, bacterial, viral, and parasitic infections. In this study, we aim to provide an update on the recent clinical and basic studies where the mechanism and function of CARD9 have been further studied and understood. In addition, we summarize the latest treatment and prevention strategies based on CARD9 and discuss the current perspectives and future direction of CARD9.
“…As detected in infectious models of acute viral myocarditis and cardiac arteritis 38 , 39 , PAMPs can induce immune responses that cause acute myocardial injury. In myocarditis induced by coxsackievirus B3 (CVB3), a single-stranded RNA virus, CARD9 -knockout (KO) mice showed less myocardial inflammation and structural disorganization 10 . In addition, CARD9 -KO mice were also protected from Candida albicans water-soluble extract (CAWS)-induced cardiac vasculitis, as evidenced by decreased vascular inflammation score 39 .…”
Section: Evidence For the Role Of Card9 In Cvdsmentioning
confidence: 99%
“…Clinically, CARD9 singlenucleotide polymorphisms have been found to be involved in autoimmune diseases, such as Crohn's disease, ulcerative colitis, ankylosing spondylitis, IgA nephropathy, and rheumatoid arthritis [6][7][8][9]. In fact, CARD9 also plays a role in both infectious and non-infectious pathophysiological processes of heart injuries, including myocarditis, myocardial ischemia reperfusion (I/R) injury, and angiotensin II (Ang II)-induced cardiac remodeling and dysfunction [10][11][12]. Previously, Tian et al summarized the proinflammatory role of CARD9 in metabolic diseases, including insulin resistance and obesity, which are the risk factors of CVDs, and in heart diseases [13].…”
Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor protein expressed on myeloid cells and located downstream of pattern recognition receptors (PRRs), which transduces signals involved in innate immunity. CARD9 deficiency is associated with increased susceptibility to various fungal diseases. Increasing evidence shows that CARD9 mediates the activation of p38 MAPK, NF-κB, and NLRP3 inflammasome in various CVDs and then promotes the production of proinflammatory cytokines and chemokines, which contribute to cardiac remodeling and cardiac dysfunction in certain cardiovascular diseases (CVDs). Moreover, CARD9-mediated anti-apoptosis and autophagy are implicated in the progression of CVDs. Here, we summarize the structure and function of CARD9 in innate immunity and its various roles in inflammation, apoptosis, and autophagy in the pathogenesis of CVDs. Furthermore, we discuss the potential therapies targeting CARD9 to prevent CVDs and raise some issues for further exploring the role of CARD9 in CVDs.
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