Journal
MUSCLE & NERVE
Volume 43, Issue 2, Pages 223-229Publisher
WILEY
DOI: 10.1002/mus.21829
Keywords
Cbl-b; CD8-positive T cells; macrophages; mice; RANTES
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Bio-Oriented Technology Research Advancement Institution of Japan
- Grants-in-Aid for Scientific Research [21590257, 22591658] Funding Source: KAKEN
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Deficiency of the Cbl-b ubiquitin ligase gene activates macrophages in mice. This study aimed to elucidate the pathophysiological roles of macrophages in muscle degeneration/regeneration in Cbl-b-deficient mice. We examined immune cell infiltration and cytokine expression in cardiotoxin-injected tibialis anterior muscle of Cbl-b-deficient mice. Ablation of the Cbl-b gene expression delayed regeneration of cardiotoxin-induced skeletal muscle damage compared with wild-type mice. CD8-positive T cells were still present in the damaged muscle on day 14 after cardiotoxin injection in Cbl-b-deficient mice, but there was dispersal of the same cells over that time-frame in wild-type mice. Infiltrating macrophages in Cbl-b-deficient mice showed strong expression of RANTES (regulated-on-activation, normal T cell expressed and secreted), a chemokine for CD8-positive T cells. In turn, a neutralizing antibody against RANTES significantly suppressed the infiltration of CD8-positive T cells into the muscle, resulting in restoration of the disturbed muscle regeneration. Cbl-b is an important regulatory factor for cytotoxic T-cell infiltration via RANTES production in macrophages. Muscle Nerve 43: 223-229, 2011
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