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P2X7-DEPENDENT SHEDDING OF HOMING AND ADHESION MOLECULAES FROM T LYMPHOCYTE REDUCES CELLULAR MIGRATION TO MUSCLES IN MDX MICE
Migração de linfócitos T
Moléculas de adesão
Inflamação
Cd44
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
Abstract
The loss of dystrophin expression leads to Duchenne muscular dystrophy (DMD), the most common form of muscular dystrophies. This genetic disorder induces muscle damage and significant secondary inflammatory injury, with muscle inflammatory foci mostly composed of macrophages and few T lymphocytes. We previously studied the scarcity of lymphoid cells in mdx mice muscles, a murine model for DMD, and published that a subpopulation of blood T lymphocyte sheds the CD62L molecule from the cell membrane. This shedding is induced by P2X7 activity and leads to reduced T lymphocyte endothelial adhesion in vitro. After P2X7 impairment in vivo, these T lymphocytes retained the selectin, homed to the cardiac muscle, and increased muscle damage. However, we did not define if the increased population of CD62L- T lymphocyte was composed of naϊve or antigen-primed cells and decided to revisit this subject. We observed that the altered phenotype is not restricted to the CD62L, as long as CD127 and CD44 are also downregulated in a P2X7-dependent manner. CD44 is a lymphocytehoming receptor that binds mainly to hyaluronan and regulates processes such as cell adhesion, angiogenesis, inflammation, cellular activation, cytoskeleton rearrangements, and others. The present results confirm and extend our previous publication and we attribute the reduced capacity of T lymphocyte homing to non-lymphoid tissues in mdx mice to a broader panel of membrane molecules affected by P2X7 activity.
Keywords in Portuguese
Distrofia Muscular de DuchenneMigração de linfócitos T
Moléculas de adesão
Inflamação
Cd44
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