Deficiency in expression of the signaling protein Sin/Efs leads to T-lymphocyte activation and mucosal inflammation.
Our studies have concentrated on elucidating the role of the signaling protein Sin in T-lymphocyte function. We have previously shown that Sin overexpression inhibits T-lymphocyte development and activation. Here we show that Sin-deficient mice exhibit exaggerated immune responses characterized by enhanced cytokine secretion and T-cell-dependent antibody production. Excessive T-cell responses in young mice correlate with spontaneous development of inflammatory lesions in different organs of aged Sin(-/-) mice, particularly the small intestine. The intestinal inflammation is characterized by T- and B-cell infiltrates in the lamina propria, which correlate with crypt enlargement and marked villus expansion and/or damage. Similar to the human intestinal inflammatory disorder Crohn's disease (CD), and in contrast to most mouse models of mucosal inflammation, inflammatory lesions in the gastrointestinal tract of Sin(-/-) mice are restricted to the small bowel. Taken together, these results suggest that Sin regulates immune system and T-lymphocyte function and that immune system dysfunction in the absence of Sin may underlie the pathogenesis of tissue-specific inflammation and enteropathies such as CD.
Donlin
Laura T
LT
Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Danzl
Nichole M
NM
Wanjalla
Celestine
C
Alexandropoulos
Konstantina
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004760:Enterocolitis / Q000235:genetics / Q000276:immunology*; D006099:Granuloma / Q000235:genetics; D007413:Intestinal Mucosa / Q000473:pathology; D008099:Liver / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; C097281:Efs protein, mouse; D010750:Phosphoproteins; D015375:Receptors, Interleukin-2