LYP regulates SLP76 and other adaptor proteins in T cells.

BACKGROUND: The LYP tyrosine phosphatase presents a SNP (1858C > T) that increases the risk of developing autoimmune diseases such as type I diabetes and arthritis. It remains unclear how this SNP affects LYP function and promotes the development of these diseases. The scarce information about LYP substrates is in part responsible for the poor understanding of LYP function. RESULTS: In this study, we identify in T lymphocytes several adaptor proteins as potential substrates targeted by LYP, including FYB, SLP-76, HS-1, Vav, SKAP1 and SKAP2. We also show that LYP co-localizes with SLP76 in microclusters, upon TCR engagement. CONCLUSIONS: These data indicate that LYP may modulate T cell activation by dephosphorylating several adaptor proteins, such as FYB, SLP-76, HS-1, Vav, SKAP1 and SKAP2 upon TCR engagement.

Immune complex-mediated tissue injury: a multistep paradigm.

Antigen-antibody complexes can damage tissues by triggering inflammation. Recent studies have enabled the description of a sequence of steps, which depend on the intra- or perivascular location of complex formation. Acute lethal toxicity and circulatory shock as a result of the acute release of inflammatory mediators can occur after intravascular complex formation. The lesions associated with perivascular complexes are characterized by plasma leakage and the recruitment of polymorphonuclear leukocytes. These lesions are modulated by mediators released from endothelial cells, namely nitric oxide, endothelins and lipid mediators, and provide an appropriate basis for the activation of both arms of hemostasis: coagulation and fibrinolysis. The balance between both activation systems can explain the late occurrence of both tissue fibrosis and organ remodeling.