Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase

Emk is a serine/threonine protein kinase implicated in regulating polarity, cell cycle progression, and microtubule dynamics. To delineate the role of Emk in development and adult tissues, mice lacking Emk were generated by t argeted gene disruption. Emk(-/-) mice displayed growth retardation and imm une cell dysfunction, Although B- and T-cell development were normal, CD4()T cells lacking Emk exhibited a marked upregulation of the memory marker C D44/pgp-1 and produced more gamma interferon and interleukin-4 on stimulati on through the T-cell receptor in vitro. In addition, B cell responses to T -cell-dependent and -independent antigen challenge mere altered in vivo. As Emk(-/-) animals aged, they developed splenomegaly, lymphadenopathy, membr anoproliferative glomerulonephritis, and lymphocytic infiltrates in the lun gs, parotid glands and kidneys. Taken together, these results demonstrate t hat the Emk protein kinase is essential for maintaining immune system homeo stasis and that loss of Emk may contribute to autoimmune disease in mammals .