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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.
IL18-family Genes Polymorphism Is Associated with the Risk of Myocardial Infarction and IL18 Concentration in Patients with Coronary Artery Disease
Published in Immunological Investigations, 2022
Anastasia V. Ponasenko, Anna V. Tsepokina, Maria V. Khutornaya, Maxim Yu. Sinitsky, Olga L. Barbarash
IL18 plays an important role in the MyD88-mediated signal. The IL18 receptor consists of the IL18 receptor accessory protein (IL18RAP) and the IL18 receptor protein (IL18R1) (Zhu et al. 2016). IL18RAP forms the signal chain of the receptor complex with IL18R1 and mediates signal transduction initiated by IL18 that stimulates IFNγ secretion (Boraschi and Dinarello 2006). IL18RAP and IL18R gene polymorphisms are associated with multiple immune-mediated diseases (Hedl et al. 2014). IL18 signaling pathway is extremely important since it is associated with the activation of the innate and adaptive immune responses that may have both protective and adverse effects. The last is mainly related to patients with long-term excessively activated or chronic inflammation.