The different faces of Notch in T-helper-cell differentiation.
Interleukin-12 (IL-12) and IL-4 induce T helper 1 (T(H)1)- and T(H)2-cell differentiation, respectively, in vitro. However, not all T(H)1-cell responses require IL-12 in vivo, and T(H)2-cell responses are remarkably independent of IL-4-receptor signalling, suggesting that other polarizing signals must exist. Accumulating evidence indicates that Notch is a candidate receptor that might mediate these signals. However, contrasting roles for Notch have been proposed: some evidence shows that Notch promotes T(H)1-cell differentiation, whereas other evidence supports a prominent role for Notch in T(H)2-cell differentiation. In this Review, we discuss recent findings that help to reconcile this discrepancy and highlight the accumulating evidence for the role of Notch in T-cell-mediated diseases.
Amsen
Derk
D
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. D.amsen@amc.uva.nl
Antov
Andrey
A
Flavell
Richard A
RA
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D006801:Humans; D038041:Lymphopoiesis; D051880:Receptors, Notch / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D051880:Receptors, Notch