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Current and Potential Applications of Pharmacogenetics and Pharmacogenomics
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Alice B. Gottlieb, Moderate to Severe Psoriasis, 2014
Rishu Gupta, Wilson Liao, John Y. M. Koo, Jashin J. Wu
In addition to polymorphisms in the TNF gene, polymorphisms in the Fc receptor affect the efficacy of TNF inhibitors by enhancing or diminishing affinity for immunoglobulin binding. In a study on rheumatoid arthritis and psoriatic arthritis, Tutuncu et al. found that clinical response to TNF blockers correlated with the Fc-γ receptor type IIIA-158 polymorphism [77]. Furthermore, Genome-Wide Association Study (GWAS) in rheumatoid arthritis have identified additional proposed markers for anti-TNF response including genes encoding transcription factors (AFF3) and cell surface membrane proteins (CD226, CD45/PTPRC) [40,83,84]. Recognition of the polymorphisms may allow practitioners to better optimize the therapeutic approach in order to maximize patient response and limit adverse effects and unnecessary costs.
Heterogeneity of T cells and macrophages in chlorine-induced acute lung injury in mice using single-cell RNA sequencing
Published in Inhalation Toxicology, 2022
Chen-qian Zhao, Jiang-zheng Liu, Meng-meng Liu, Xiao-ting Ren, De-qin Kong, Jie Peng, Meng Cao, Rui Liu, Chun-xu Hai, Xiao-di Zhang
The cellular communication between T cells and macrophages was evaluated by the R software packages ‘CellChat’ and ‘cellphoneDB’ (Vento-Tormo et al. 2018; material details) (Figure 8(A,B)). We found that the strongest interaction between T cells and macrophages in the control group occurred between C-6 T cells and Mø-2 macrophages (Figure 8(C)). Interactions between T cells and macrophages were higher in the Cl2-exposed group compared to the control group, particularly C-6 for T cells and Mø-5 or 6 for macrophages (Figure 8(D)). Next, our analysis further determined the different receptor-ligand interactions in the two groups. We discovered that the frequency of receptor-ligand interactions between T cells and macrophages differed significantly between the control and Cl2-exposed groups (Figure 8(E,F)). The Cl2-exposed group showed a high degree of inflammatory response, manifested as the expression of pro-inflammatory-related receptor ligands CD74-Copa, CD74-App, Il18 receptor-Il18, Il33 receptor-Il33, and Il15 receptor-Il15 (Figure 8(F,G)). However, it is worth noting that a small subset of anti-inflammatory-related receptor ligands were also expressed, such as Mrc1-Ptprc and CD44-Spp1 (Figure 8(F,G)).
A novel role for an old target: CD45 for breast cancer immunotherapy
Published in OncoImmunology, 2021
Annat Raiter, Oran Zlotnik, Julia Lipovetsky, Shany Mugami, Shira Dar, Ido Lubin, Eran Sharon, Cyrille J. Cohen, Rinat Yerushalmi
We revealed that C24D binds to the CD45 receptor on T and NK cells. CD45 is a transmembrane protein tyrosine phosphatase receptor type C (PTPRC), with double opposing effects on T cell receptor (TCR) activity.17 On the one hand, CD45 plays an inhibitory function involving the dephosphorylation of the tyrosine 394 (Y394) in the lymphocyte-specific protein tyrosine kinase (Lck), preventing its activation.18 On the other hand, CD45 plays the role of activator when it dephosphorylates the tyrosine 505 (Y505), an inhibitory site at the C-terminal end of the non-receptor tyrosine-Src kinases. Activated Lck phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) of the T cell receptor (TCR)/CD3 complex. The phosphorylated ITAMs recruit the Zeta-chain-associated protein kinase 70 (ZAP-70), via its Src homology 2 (SH2) domains. Finally, for TCR activation, CD3-bound ZAP-70 is activated by both Lck and (trans)-autophosphorylation at the ZAP-70 tyrosine 493 (Y493).19 Downstream of protein tyrosine kinases is located the proto-oncogene VAV. Ligation of the activating receptor NKG2D on human NK cells results in phosphorylation of the signaling chain DAP10 by Src family kinases and the recruitment of VAV-1. VAV-1 is then phosphorylated by Src family kinases, as required for NK cell activation.20
Single-cell analysis reveals immune modulation and metabolic switch in tumor-draining lymph nodes
Published in OncoImmunology, 2020
Yen-Liang Li, Chung-Hsing Chen, Jing-Yi Chen, You-Syuan Lai, Shao-Chun Wang, Shih-Sheng Jiang, Wen-Chun Hung
We next examined the relation between those DEGs and markers of the status characteristics of cells including polarization, proliferation, activation and differentiation. A total of 28 genes were selected as markers for those characteristics (Supplementary Table S1). At q < 0.1, significant DEGs among those markers were shown in the volcano plot figure 2f. For CD4 + T cells, all markers of proliferation (Cxcr4), polarization (Cxcr4, Tgfb1 and Cd4), and differentiation (Cd74 and Cd4) were significantly downregulated in TDLNs samples. For CD8 + T cells, only differentiation marker Cd74 was found and downregulated significantly. For Treg cells, Ptprc, also known as Cd45, a marker for both proliferation and differentiation, was found significantly upregulated. Since Cd45 has been known for its role in Treg activation,40 the upregulation of Cd45 expression could implicate increase in the activity of Treg cells in TDLNs.