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%) develop a spontaneous lymphoproliferative disease (LPD) that results in dramatic splenomegaly. The cell populations observed in the LPD spleens can be divided into 2 categories, those that are composed of mixed lineage cells and those that are predominantly T cells with a phenotype similar to that in autoimmune lymphoproliferative syndrome (ALPS) patients. These data suggest that while active STAT6 is not a transforming factor, expression in T cells predisposes toward the development of lymphoproliferative disorders.
Kaplan
Mark H
MH
Department of Pediatrics, Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. mkaplan2@iupui.edu
Sehra
Sarita
S
Chang
Hua-Chen
HC
O'Malley
John T
JT
Mathur
Anubhav N
AN
Bruns
Heather A
HA
D000818:Animals; D019070:Cell Lineage; D004198:Disease Susceptibility; D008232:Lymphoproliferative Disorders / Q000209:etiology*; D051379:Mice; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D013154:Spleen / Q000473:pathology; D013163:Splenomegaly; D013601:T-Lymphocytes / Q000473:pathology
D050800:STAT6 Transcription Factor