Función fisiológica sobre la respuesta inmune e inflamatoria de la molécula inducible durante la activación leucocitaria CD69
Author
Sancho Madrid, DavidAdvisor
Sánchez Madrid, FranciscoEntity
UAM. Departamento de Biología MolecularDate
2001-11-17Subjects
Antígenos CD - Tesis doctorales; Linfocitos T - Tesis doctorales; Biología y Biomedicina / BiologíaNote
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 17-11-2001Abstract
CD69 is a C-type lectin early induced following activation of leukocytes. Structurefunction
relationship studies have shown that the ligand binding and the signal transduction
domains of CD69 and snother C-type lectin, CD23, function independently and the signal
transduced depends on the cytoplasmic tail. In other studies about CD69 induction, we found that interaction of the T lymphocyte with endothelium h g h the LFA-I/lCAM-1 palhway increases CD69 expression. This effect is additive to tite stimulation provided by L-15. To investigate the possible role of CD69 in viva, CD69 deficient mice were generated and analyzed. Positive and negative selection at thymus was not affected CD69 deficiency leaded to a sligbt increment in pre-B ceh at bone marrow and a significant increase in the Tdependent B ceU response. CD69 is highly expressed by leukocytes at intiammatory sites, but its physiological mle during inflammation remains unlaiown. The tole of CD69 in the autoimmune reactivity was explored in a model of collagen-induced arthntis (CIA) in wild type and CD69-deficient mice. CD69 mice showed higher incidence and severity of CIA. with exacerbated T and B immune responss to type 11 coilagen. Transf&g growth factor (TGF)-beta 1 and 2. which act as protective in CIA. were reduced inCD69 mice inflammatoq foci, correlating wilh an inmase in some pminflammatory cytolanes. Local injection of blocking anti-TGF-beta antibodies increased CIA severity and proinfiammatory cytoLine mRNA levels in ~ ~ 6 9 + /b+ut, not in ~ ~ 6 m9ic"e. In addition, the treatment with anti-CD69 blocking antibodies in viva confinned the negative regulatory role of CD69 through n;F-be@-related mechanisms in an independent CIA model using DBAII mice. Moreover, in v&ra engagement of CD69 induced mtal and active TGF-betal prcduction. Our
resulis show that CD69 is a negative modulator of autoimmune reactivity aod iaflamrmrtion h g b th e synibesis of TGF-beta, a cytokine thai in tun~do wn-regulates the pmduuion of different pro-inflammatory mediatas.
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