T-cell activation, alterations in systemic lupus erythematosus: A narrative review

The activation of T cells is initiated by the presentation of exogenous or endogenous antigens, by antigen presenting cells through the major histocompatibility complex, which binds to a special receptor on T cells. This acknowledgement triggers a cascade of intracellular signalling that leads to an increase in integrin expression, cytoskeletal modifications, and transcription factors production involved in the liberation of cytokines and inflammatory mediators. One of the most important inducers in cell activation is the enzymatic complex with tyrosine kinase action. The kinases which belong to the SRC (SFK) LCK and FYN family have been involved in a large number of important processes in the activation and modulation of the T cells response, as well as in the development of autoimmune diseases. Regulating the kinases signalling, as well as the adapter proteins involved in T cell activation, is essential for maintaining an activation threshold, as well as the modulation of cell response. The phosphorylation of the positive regulation sites of these proteins is important to allow an active configuration of the protein and thereby its maximum capacity as kinase. The phosphorylation of negative regulation sites leads to a closed configuration of the protein that reduces its kinase function, and thereby inhibits its own function. The alteration in signalling by the modification of certain cytoplasmic proteins in some cases is associated with the development of autoimmune diseases, such as systemic lupus erythematosus. Under physiological conditions the T cell receptor complex regroups with protein complexes that interact harmonically to generate an internal signal. The altered signalling events are partly responsible for an anomalous expression of cytokines, including the interleukin-6 (IL-6), IL-10, IL-2, IFN, and CD40 linking, these modifications affects the cells ability to over-stimulate T and B cells, resulting in an increased production of autoantibodies and the triggering of the autoimmune disease. © 2017 Asociación Colombiana de Reumatología

• Fecha de publicación: 2018
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: spa
• OAI Identifier: oai:repository.urosario.edu.co:10336/23078
• Acceso en línea: https://doi.org/10.1016/j.rcreu.2017.07.002; https://repository.urosario.edu.co/handle/10336/23078
• Palabra clave: Adaptor protein; Autoantibody; Major histocompatibility antigen; Protein tyrosine kinase; T lymphocyte receptor; Antibody production; Antigen presentation; Antigen presenting cell; Autoimmune disease; Cell function; Cell stimulation; Complex formation; Cytokine release; Enzyme activity; Human; Inflammation; Intracellular signaling; Protein binding; Protein expression; Protein function; Protein phosphorylation; Regulatory mechanism; Short survey; Systemic lupus erythematosus; T lymphocyte activation; Immuno receptor tyrosine-based activation motif; Leukocyte c-terminal src kinase; Linker for activation of t cell; Systemic lupus erythematosus; T-cell receptor; Zeta-chain t-cell receptor associated protein kinase 70kda; src family tyrosine kinase; Fyn proto-oncogene
• License: Abierto (Texto Completo)