Defective T-lymphocyte migration to muscles in dystrophin-deficient mice

dc.creatorCascabulho, Cynthia M.
dc.creatorCorrêa, Cristiane Bani
dc.creatorAlmeida, Vinicius Cotta de
dc.creatorPons, Andrea Henriques
dc.date2017-04-11T14:56:40Z
dc.date2017-04-11T14:56:40Z
dc.date2012
dc.date.accessioned2023-09-26T23:49:07Z
dc.date.available2023-09-26T23:49:07Z
dc.identifierCASCABULHO, Cynthia M. et al. Defective T-Lymphocyte Migration to Muscles in Dystrophin-Deficient Mice. The American Journal of Pathology, v.181, n.2, p.593-604, August 2012
dc.identifier0002-9440
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/18377
dc.identifier10.1016/j.ajpath.2012.04.023
dc.identifier1525-2191
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8894544
dc.descriptionDuchenne muscular dystrophy (DMD), an X-linked recessive disorder affecting 1 in 3500 males, is caused by mutations in the dystrophin gene. DMD leads to degeneration of skeletal and cardiac muscles and to chronic inflammation. The mdx/mdx mouse has been widely used to study DMD; this model mimics most characteristics of the disease, including low numbers of T cells in damaged muscles. In this study, we aimed to assess migration of T cells to the heart and to identify any alterations in adhesion molecules that could possibly modulate this process. In 6-week-old mdx/mdx mice, blood leukocytes, including T cells, were CD62L(+), but by 12 weeks of age down-modulation was evident, with only approximately 40% of T cells retaining this molecule. Our in vitro and in vivo results point to a P2X7-dependent shedding of CD62L (with high levels in the serum), which in 12-week-old mdx/mdx mice reduces blood T cell competence to adhere to cardiac vessels in vitro and to reach cardiac tissue in vivo, even after Trypanosoma cruzi infection, a known inducer of lymphoid myocarditis. In mdx/mdx mice treated with Brilliant Blue G, a P2X7 blocker, these blood lymphocytes retained CD62L and were capable of migrating to the heart. These results provide new insights into the mechanisms of inflammatory infiltration and immune regulation in DMD.
dc.description2030-01-01
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectDistrofia Muscular de Duchenne
dc.subjectMigração defeituosa de linfócitos T
dc.subjectRatos
dc.subjectDuchenne muscular dystrophy
dc.subjectmice
dc.subjectDefective T-Lymphocyte Migration
dc.titleDefective T-lymphocyte migration to muscles in dystrophin-deficient mice
dc.typeArticle


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