Hyperactivation and proliferation of lymphocytes from the spleens of flaky skin (fsn) mutant mice.
Mice homozygous for the flaky skin (fsn) single gene mutation have a severe hyperproliferative disease resulting in a complex phenotype, which includes widespread inflammation and autoimmunity. This study sought to characterize lymphocyte function of flaky skin mutant mice. Flaky skin lymphocytes show enhanced proliferation with in vitro mitogen stimulated spleen cells, as well as enriched splenic B- and T-cells. The production of IL-4 by fsn/fsn T-lymphocytes is increased dramatically compared with normal controls. Flaky skin lymphocytes exhibited increased responsiveness to IL-2, IL-4 and IL-7 in the absence of pre-activation, enhanced IgE production in response to ovalbumin immunization, and constitutive STAT6 activation. These data indicate that the cytokines IL-2, IL-4 and IL-7 likely contribute to the lymphocyte activation in fsn/fsn mutant mice. This lymphocyte hyperactivation may result in the development of systemic autoimmunity in fsn/fsn mutant mice.
Welner
Robert
R
Department of Applied Medical Sciences, University of Southern Maine, Portland, ME 04104-9300, USA.
Hastings
William
W
Hill
Beth L
BL
Pelsue
Stephen C
SC
D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000378:metabolism*; D049109:Cell Proliferation; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D015851:Interleukin-7 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D050800:STAT6 Transcription Factor; D013154:Spleen; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
D007376:Interleukin-2; D015851:Interleukin-7; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4