No abstract

Tissue transglutaminase (TGase2) is a protein-crosslinking enzyme known to be associated with the in vivo apoptosis program. Here we report that apoptosis could be induced in TGase2 ؊/؊ mice; however, the clearance of apoptotic cells was defective during the involution of thymus elicited by dexamethasone, anti-CD3 antibody, or ␥-irradiation, and in the liver after induced hyperplasia. The lack of TGase2 prevented the production of active transforming growth factor-␤1 in macrophages exposed to apoptotic cells, which is required for the up-regulation of TGase2 in the thymus in vivo, for accelerating deletion of CD4؉CD8؉ cells and for efficient phagocytosis of apoptotic bodies. The deficiency is associated with the development of splenomegaly, autoantibodies, and immune complex glomerulonephritis in TGase2 ؊/؊ mice. These findings have broad implications not only for diseases linked to inflammation and autoimmunity but also for understanding the interrelationship between the apoptosis and phagocytosis process.

Kovács et al. examine the role of the Src family kinases Hck, Fgr, and Lyn in immune cell–mediated inflammation. Using arthritis and skin inflammation models, the authors show that mice lacking hematopoietic Hck, Fgr, and Lyn are protected from these inflammatory diseases, showing loss of myeloid cell recruitment and lack of inflammatory mediator production. Unexpectedly, the three kinases are dispensable for the intrinsic migratory ability of myeloid cells. These finding may have clinical implications in rheumatic and skin diseases.