TYK2 in Immune Responses and Treatment of Psoriasis

Shang, Lin; Cao, Jiali; Zhao, Siqi; Zhang, Jingya; He, Yanling

doi:10.2147/jir.s380686

Cited by 14 publications

(12 citation statements)

References 86 publications

(116 reference statements)

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“…TYK2 acted as an integral part of the differentiation of innate immune cells and immune response, regulating the release of pro-inflammatory cytokines such as type I IFN and IL-6. When TYK2 is induced to be expressed, it will further lead to the activation of STAT1 and STAT4 [59]. In TYK2 and STAT1-deficient mouse macrophages, the induction of the pro-inflammatory cytokine IFN-β by LPS was severely reduced [60].…”

Section: Dietary Isct Attenuates the Inflammatory Response Associated...mentioning

confidence: 99%

Isalo scorpion cytotoxic peptide‐strengthened immune function through the JAKs/STATs signaling pathway of the immune organ of grass carp (Ctenopharyngodon idella) challenged with Aeromonas hydrophila

He,

Hu,

Zhou

et al. 2024

Animal Research and One Health

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To investigate the impact of Isalo scorpion cytotoxic peptide (IsCT) on the immune function of immune organ (head kidney, spleen, and skin) of grass carp (Ctenopharyngodon idella), 540 fish (136.88 ± 0.72 g) were supplied with a different amount of IsCT (0, 0.6, 1.2, 1.8, 2.4, and 3.0 mg/kg diet) through a period of 60 days. Afterward, 24 fish were randomly selected from each group and were inoculated with Aeromonas hydrophila for a period of 6 days. Our findings suggested that appropriate IsCT complementation: (1) attenuated skin morbidity and histopathological structural changes in the head kidney and spleen (p < 0.05), which ensured the structural integrity of the immune organs; (2) increased the activity and expression of immune substances (p < 0.05), which in turn increased the function of the immune organs, promoting immune responses; (3) through the regulation of the Janus kinase/signal transducers and activators of transcription (JAKs/STATs) signaling pathway, the mRNA expression of anti‐inflammatory cytokines increased and the mRNA expression of pro‐inflammatory cytokines decreased, which in turn increased the function of the immune organs, reducing the inflammatory response (p < 0.05). However, the addition of IsCT did not affect the expression of IL‐12p35, STAT2, and STAT3a in the immune organ. Ultimately, this study provided evidence that IsCT enhanced immune function via the JAKs/STATs signaling pathway in the immune organ in grass carp after challenged with Aeromonas hydrophila.

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Section: Dietary Isct Attenuates the Inflammatory Response Associated...mentioning

confidence: 99%

Isalo scorpion cytotoxic peptide‐strengthened immune function through the JAKs/STATs signaling pathway of the immune organ of grass carp (Ctenopharyngodon idella) challenged with Aeromonas hydrophila

He,

Hu,

Zhou

et al. 2024

Animal Research and One Health

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“…This can be explained by the implication of Tyk2 in multiple pathways related to psoriasis. The inflammatory environment of active psoriatic skin lesions is characterized by the expression of Th1- and Th17-related cytokines, and type I IFN, IL-6, IL-10, IL-12, IL-22, and IL-23 are only a few of the pathogenetically relevant cytokines with signaling pathways affected by Tyk2 loss-of-function mutations ( Figure 3 ) [ 8 , 10 , 22 , 23 ]. Inhibiting Tyk2 activation might be associated with an ideal balance between efficacy and safety because individuals with deactivating genetic variants of Tyk2 are highly protected from some IMIDs but do not exhibit an increased risk of hospitalization for mycobacterial, viral, or fungal infections [ 23 , 24 , 25 , 26 , 27 ].…”

Section: Tyk2 Signaling and Pathogenetic Implicationsmentioning

confidence: 99%

“…These Jak dimers phosphorylate the receptor, allowing the attachment, phosphorylation, and eventual dimerization of STAT proteins (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) ( Figure 1 ). Activated STAT proteins combine to form dimers and can translocate to the nucleus where they can act as transcription factors, upregulating the genes responsible for production of proinflammatory cytokines and growth factors, or regulate the behavior of other intracellular proteins [ 1 , 3 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Tyk2 Targeting in Immune-Mediated Inflammatory Diseases

Rusiñol

Puig

2023

IJMS

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The Janus kinase (Jak)/signal transducer and activating protein (STAT) pathways mediate the intracellular signaling of cytokines in a wide spectrum of cellular processes. They participate in physiologic and inflammatory cascades and have become a major focus of research, yielding novel therapies for immune-mediated inflammatory diseases (IMID). Genetic linkage has related dysfunction of Tyrosine kinase 2 (Tyk2)—the first member of the Jak family that was described—to protection from psoriasis. Furthermore, Tyk2 dysfunction has been related to IMID prevention, without increasing the risk of serious infections; thus, Tyk2 inhibition has been established as a promising therapeutic target, with multiple Tyk2 inhibitors under development. Most of them are orthosteric inhibitors, impeding adenosine triphosphate (ATP) binding to the JH1 catalytic domain—which is highly conserved across tyrosine kinases—and are not completely selective. Deucravacitinib is an allosteric inhibitor that binds to the pseudokinase JH2 (regulatory) domain of Tyk2; this unique mechanism determines greater selectivity and a reduced risk of adverse events. In September 2022, deucravacitinib became the first Tyk2 inhibitor approved for the treatment of moderate-to-severe psoriasis. A bright future can be expected for Tyk2 inhibitors, with newer drugs and more indications to come.

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“…The JAK/STAT signaling pathway comprises an extended protein network that facilitates the secretion of an abundance of pro-inflammatory cytokines as well as growth factors and thus poses an ideal therapeutic target for psoriasis [ 99 ]. Indeed, JAK and TYK2 inhibitors are a class of medications that block Janus kinases and downstream products, showing an efficacious inhibition of pathogenic signaling pathways, including IL-23 ( Figure 1 ).…”

Section: Small Moleculesmentioning

confidence: 99%

Pharmaco-Omics in Psoriasis: Paving the Way towards Personalized Medicine

Antonatos

Asmenoudi

Panoutsopoulou

et al. 2023

IJMS

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The emergence of high-throughput approaches has had a profound impact on personalized medicine, evolving the identification of inheritable variation to trajectory analyses of transient states and paving the way for the unveiling of response biomarkers. The utilization of the multi-layered pharmaco-omics data, including genomics, transcriptomics, proteomics, and relevant biological information, has facilitated the identification of key molecular biomarkers that can predict the response to therapy, thereby optimizing treatment regiments and providing the framework for a tailored treatment plan. Despite the availability of multiple therapeutic options for chronic diseases, the highly heterogeneous clinical response hinders the alleviation of disease signals and exacerbates the annual burden and cost of hospitalization and drug regimens. This review aimed to examine the current state of the pharmaco-omic approaches performed in psoriasis, a common inflammatory disease of the skin. We sought to identify central studies that investigate the inter-individual variability and explore the underlying molecular mechanisms of drug response progression via biological profiling in psoriatic patients administered with the extended therapeutic armamentarium of psoriasis, incorporating conventional therapies, small molecules, as well as biological drugs that inhibit central pathogenic cytokines involved in the disease pathogenesis.

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TYK2 in Immune Responses and Treatment of Psoriasis

Cited by 14 publications

References 86 publications

Isalo scorpion cytotoxic peptide‐strengthened immune function through the JAKs/STATs signaling pathway of the immune organ of grass carp (Ctenopharyngodon idella) challenged with Aeromonas hydrophila

Isalo scorpion cytotoxic peptide‐strengthened immune function through the JAKs/STATs signaling pathway of the immune organ of grass carp (Ctenopharyngodon idella) challenged with Aeromonas hydrophila

Tyk2 Targeting in Immune-Mediated Inflammatory Diseases

Pharmaco-Omics in Psoriasis: Paving the Way towards Personalized Medicine

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