T-cell effector pathways in allergic diseases: transcriptional mechanisms and therapeutic targets.
Originally interpreted within the framework of a binary T(H)1/T(H)2 paradigm, our knowledge of the pathogenesis of atopic diseases has broadened to incorporate the contribution of T regulatory cells and the newly described proinflammatory T(H)17 cell lineage. The commitment of peripheral T-cell clones to undergo differentiation into one of those lineages is shaped by self-reinforcing transcriptional circuitries that center on key transcriptional regulators: T-box expressed in T cells (T(H)1), GATA-3 (T(H)2), forkhead box p3 (T regulatory cells), and retinoid-related orphan receptor gammatau/retinoid-related orphan receptor alpha (T(H)17). These circuits function both to establish the respective lineage phenotype and to enable epigenetic changes that maintain those phenotypes long-term. This evolving view of how signaling and transcriptional networks generate effector T-cell responses suggests novel therapeutic approaches to reprogram effector T-cell lineage commitment in allergic diseases in favor of tolerance induction.
Chatila
Talal A
TA
Division of Immunology, Allergy and Rheumatology, Department of Pediatrics, University of California at Los Angeles, Los Angeles, CA, USA. tchatila@mednet.ucla.edu
Li
Ning
N
Garcia-Lloret
Maria
M
Kim
Hyon-Jeen
HJ
Nel
Andre E
AE
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D016503:Drug Delivery Systems; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*
D018836:Inflammation Mediators; D014157:Transcription Factors