Constitutively active STAT6 predisposes towards a lymphoproliferative disorder

Constitutively active STAT6 predisposes toward a lymphoproliferative disorder.

Signal transducer and activator of transcription 6 (STAT6) is critical for IL-4 and IL-13 responses, and necessary for the normal development of Th2 cells. We previously generated mice that express a constitutively active STAT6 (STAT6VT) under control of the CD2 locus control region, which directs expression to the T-cell compartment. We now describe that a small proportion of these mice (~5%) ...

STAT6 deletion converts the Th2 inflammatory pathology afflicting Lat(Y136F) mice into a lymphoproliferative disorder involving Th1 and CD8 effector T cells.

Mutant mice in which tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (Lat(Y136F) mice) develop a lymphoproliferative disorder involving polyclonal CD4 effector T cells that produce massive amounts of IL-4 and trigger severe Th2 inflammation. Naive CD4 T cells can themselves produce IL-4 and thereby initiate a self-reinforcing positive regulatory loop tha...

STAT6 Deletion Converts the Th2 Inflammatory Pathology Afflicting Lat Mice into a Lymphoproliferative Disorder Involving Th1 and CD8 Effector T Cells

IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6.

IL-4 is required for the pathogenesis of atopic diseases and immune regulation. Stat6 is critical for IL-4-induced gene expression and Th cell differentiation. Recently, we have generated mice expressing a mutant Stat6 (Stat6VT) under control of the CD2 locus control region that is transcriptionally active independent of IL-4 stimulation. To determine whether active Stat6 in T cells is sufficie...

Distinct Effects in T and B Cells Vivo Alters Lymphocyte Homeostasis with Expression of a Constitutively Active Stat6 In