The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37

Kowallik, Sarah; Kritikos, Andreas; Kästle, Matthias; Thurm, Christoph; Schraven, Burkhart; Simeoni, Luca

doi:10.3390/ijms22010126

Cited by 2 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the activation of the CLEC signaling pathway may inhibit the cytotoxic effects of CD8+ T cells (32). CD99, LCK, and MHC-1 signaling pathways all regulate the proliferation and differentiation of CD8+ T cells and CD16+ NK cells (33)(34)(35). Additionally, the ITGB2 and CCL signaling pathways have adhesive and chemotactic effects and mediate the in ltration of CD8+ T and CD16+ NK cells (36, 37).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of inflammatory cells reveals novel molecular typing of biliary atresia

Zheng

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Objectives: Biliary Atresia (BA) is a severe cholangiopathy that affects the liver's bile ducts in pediatric patients. Ongoing research has identified a range of factors that may be contributing to the development of BA, with inflammation and fibrosis being among the most widely studied. However, it is essential to acknowledge that not all patients present with these etiological mechanisms. The significance of inflammation-associated cells as a contributing factor in BA is increasingly being recognized. Our approach to re-classifying BA involves integrating gene microarray data and scRNA-seq data, enabling us to provide customized clinical treatment and facilitating mechanistic studies. Methods: The BA microarray dataset GSE15235, containing gene expression data from BA and normal liver, was downloaded from the Gene Expression Omnibus (GEO) database. To validate our findings, we used an additional dataset (GSE46960) as a replication cohort. By analysis of the immune microenvironment, eight types of inflammation-associated immune cells were used for typing research. The combination of enrichment analysis and clinical data revealed the characteristics of each subtype. An effective method for identifying BA typing through machine learning algorithms. The immune landscape of biliary atresia T and NK cells was further analyzed by combining scRNA-seq datasets. Results: Two novel subtypes of inflammation were identified, the highly immune-activated C1 subtype and the lowly immune-activated C2 subtype. The C1 subtype exhibits an enhanced inflammatory response accompanied by a high infiltration of neutrophils and macrophages M1. On the other hand, the C2 subtype exhibits cell cycle activation, enhanced lipid metabolic activity, and stronger fibrosis accompanied by a high infiltration of CD8+ T cells and NK cells. CD8+ T cells may promote value-added and differentiation through signaling pathways such as CD99, CLEC, and ITGB2, further leading to fibrosis. Conclusion: In conclusion, we have defined two novel inflammatory subtypes and offered the possibility to identify and treat them. The role of neutrophils, CD8+ T cells, and CD16+ NK cells in BA deserve to be further explored.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of inflammatory cells reveals novel molecular typing of biliary atresia

Zheng

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Lck is usually involved in the TCR signaling initiation, which determines T cell antigen specificity (Kowallik et al, 2020). The TCR…”

Section: Lck-nf-κb Signaling Pathway In Physiologymentioning

confidence: 99%

New insights into the Lck-NF-κB signaling pathway

Zhang

Wu²,

Hu³

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Lck is essential for the development, activity, and proliferation of T cells, which may contribute to pathological progression and development of human diseases, such as autoimmune disorders and cancers when functioning aberrantly. Nuclear factor-κB (NF-κB) was initially discovered as a factor bound to the κ light-chain immunoglobulin enhancer in the nuclei of activated B lymphocytes. Activation of the nuclear factor-κB pathway controls expression of several genes that are related to cell survival, apoptosis, and inflammation. Abnormal expression of Lck and nuclear factor-κB has been found in autoimmune diseases and malignancies, including rheumatoid arthritis, systemic lupus erythematosus, acute T cell lymphocytic leukemia, and human chronic lymphocytic leukemia, etc. Nuclear factor-κB inhibition is effective against autoimmune diseases and malignancies through blocking inflammatory responses, although it may lead to serious adverse reactions that are unexpected and unwanted. Further investigation of the biochemical and functional interactions between nuclear factor-κB and other signaling pathways may be helpful to prevent side-effects. This review aims to clarify the Lck-nuclear factor-κB signaling pathway, and provide a basis for identification of new targets and therapeutic approaches against autoimmune diseases and malignancies.

show abstract

The Activity and Stability of p56Lck and TCR Signaling Do Not Depend on the Co-Chaperone Cdc37

Cited by 2 publications

References 43 publications

Comprehensive characterization of inflammatory cells reveals novel molecular typing of biliary atresia

Comprehensive characterization of inflammatory cells reveals novel molecular typing of biliary atresia

New insights into the Lck-NF-κB signaling pathway

Contact Info

Product

Resources

About