China
Africa
Explore chapters and articles related to this topic
Celiac disease
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Most of the established loci harbor candidate genes with immune functions. These genes can be classified into different pathways. Many of the genes belong to pathways of T- and B-cell costimulation. Such genes include CTLA4, CD80, SH2B3, PTPN2, TAGAP, ICOSLG, and CD247. Also frequently represented are cytokine and cytokine receptor genes, including IL2/IL21, IL12A, and IL18RAP; genes involved in migration of immune cells such as the chemokine receptors CCR3/CCR5/CCR1 and CCR4; and the integrin gene ITGA4. Another interesting pathway involves molecules important for T-cell development in the thymus, such as THEMIS, which plays a role in both positive and negative T-cell selection during late thymocyte development, and RUNX3, which is involved in CD8+ T-cell differentiation. One network includes genes involved in nuclear factor (NF)-κB signaling, such as REL, which encodes a component of the NF-κB complex, and TNFAIP3, which encodes a molecule that inhibits NF-κB activity. Finally, a pathway involving molecules implicated in innate immune detection such as toll-like receptor 7 (TLR7), TLR8, and IRF4 has been identified. Both TLR7 and TLR8 recognize viral RNA, whereas IRF4 is a transcriptional activator that is part of the TLR7 pathway. This latter finding suggests involvement of viruses in the pathogenesis of celiac disease, likely initial events important for inducing the antigluten CD4+ T-cell response.
Scleroderma and associated complications
Published in Biju Vasudevan, Rajesh Verma, Dermatological Emergencies, 2019
Yasmeen Jabeen Bhat, Safiya Bashir
A number of gene alleles have been linked to disease susceptibility and clinical features, which include transforming growth factor-β (TGF-β), monocyte chemoattractant protein-1 (MCP-1), interleukin-1a (IL-1a), tumor necrosis factor-α (TNF-α), connective tissue growth factor (CTGF), fibrillin-1, interferon regulatory factor-5 (IRF-5), signal transducer, and activator-4 [8]. The association of HLA B8 with severe cases [9], and the presence of raised DR2, DR5, and anticentromere antibodies with mild cases of systemic sclerosis have also been determined. HLA-DRB1*11–DQB1*0301 haplotypes have been associated with antitopoisomerase I positivity, whereas HLA-DRB1*01–DQB1*0501 haplotypes are more common in anticentromere antibodies (ACA) positive patients [10]. Multiple susceptibility loci for systemic sclerosis have also been identified at non-HLA regions such as STAT4, TNFSF4, CD247, and MIF [11].
CD3Z polymorphisms and promoter hypermethylation in dermatomyositis - the role of cytosine-phosphate-guanine-related single nucleotide polymorphisms
Published in Immunological Investigations, 2022
Radoslava Saraeva, Zornitsa Kamenarska, Lyubomir Dourmishev, Anton Vinkov, Gyulnas Dzhebir, Darina Kachakova, Neviana Ivanova, Joana Pozharashka, Radka Kaneva, Maria Hristova
Recently, genome-wide association studies have identified CD247 as a novel genetic risk factor for the susceptibility to systemic sclerosis (Radstake et al. 2010), celiac disease, and rheumatoid arthritis (Zhernakova et al. 2011). The expression of CD247 was studied in SLE patients and was found to be significantly lower compared to healthy controls (Gorman et al. 2008; Takeuchi et al. 2004). The two SNPs rs1052230 G > C and rs1052231 T > A in the 3ʹUTR of the gene were found to affect the CD247 expression level in both SLE patients and healthy controls. However, no association was found between the individual polymorphisms and the development of SLE in European (Gorman et al. 2008; Hristova et al. 2017), Chinese (Li et al. 2012) and multiethnic cohorts (Martins et al. 2015). Searching for an explanation of those discrepancies, apart from population differences, we performed a haplotype analysis. However, the results show no association of the CD247 polymorphisms either individually or as haplotypes with the development of DM. The only associations that we found were with some clinical manifestations of DM such as photosensitivity and cutaneous disease. Those findings are similar to earlier data showing that low secreting CD247 alleles and genotypes could influence the clinical manifestations of some autoimmune diseases such as SLE (Hristova et al. 2017; Li et al. 2012) and rheumatoid arthritis (RA) (Teruel et al. 2013). These results confirm the hypothesis that the two polymorphisms are associated with the severity rather than with the disease and also give rise to a question for possible modifying factors in the field of epigenetics as an underlying mechanism.
MDSCs interactions with other immune cells and their role in maternal-fetal tolerance
Published in International Reviews of Immunology, 2022
Yi Zhang, Xiaoya Wang, Rongchao Zhang, Xi Wang, Haiying Fu, Wei Yang
Currently, some studies have attempted to clarify the mechanisms of the inhibitory effect of MDSCs on NK cells. Andrew Stiff et al. studied the effect of MDSCs on the FcR-mediated function of NK cells by coculturing autologous NK cells and MDSCs from cancer patients, and they found that the nitric oxide produced by MDSCs participates in the inhibition of NK cell function [52]. Moreover, inhibiting the production of nitric oxide enhances the FcR-mediated function of NK cells. This finding indicates that MDSCs inhibit FcR-mediated NK cell functions through NO, including ADCC, cytokine production and signal transduction [52]. In addition, Dhifaf Sarhan et al. cocultured MDSCs and NK cells from patients infected with cytomegalovirus (CMV) and found that this NK cell expressed a lower level of inhibitory receptor TIGIT, thereby resisting MDSC-mediated immune suppression [53]. The mechanism is that TIGIT signal transduction causes the phosphorylation of ZAP70/Syk and ERK1/2 to decrease. These effects can be reversed by blocking TIGIT on NK cells or by inhibiting the production of ROS by MDSCs, which leads to a significant decrease in the expression of the TIGIT ligand CD155 on MDSCs. This result suggests that TIGIT/CD155 is the key molecule for MDSCs to inhibit NK cells, and NK cells induced by the CMV virus have low expression of TIGIT, resulting in a decrease in the inhibitory effect of MDSCs [53]. In fact, as early as a review in 2016, two other key molecules were mentioned, CD247 and NKG2D (killing lectin-like receptor (KLR), which can initiate the killing effect of NK cells), on the surface of NK cells. MDSCs can downregulate CD247 and NKG2D on the surface of NK cells. The former is the key subunit of the natural cytotoxicity receptors (NCRs) NKp46, NKp30 and FcγRIII [53]. Low expression of CD247 inhibits the development and cytotoxic activity of NK cells; it can trigger the killing effect of NK cells, and its low expression inhibits the killing effect of NK cells. It is worth noting that, when the expression of NK cells on MDSCs is blocked, the inhibitory effect of MDSCs on NK cells is reversed, indicating that the inhibitory effect might depend on the contact between cells [53]. To date, many studies have shown the inhibitory effect of MDSCs on NK cells, but there have been few studies on whether NK cells have an effect on MDSCs. The reason for this phenomenon might be the complex interactions between cells and the complex influencing factors in the environment. Therefore, it is not clear whether NK cells are counterproductive (inhibition), nor is it clear how to inhibit the effect of MDSCs.