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Transforming growth factor-beta: Recent advances on its role in immune tolerance.
Methods Mol. Biol. 677, 303-338 (2011)
Transforming growth factor (TGF-β1) is a pleiotropic cytokine, secreted by immune and nonhematopoietic cells. TGF-β is involved in many different critical processes, such as embryonal development, cellular maturation and differentiation, wound healing, and immune regulation. It maintains immune homeostasis by acting as a potent immune suppressor through inhibition of proliferation, differentiation, activation, and effector function of immune cells. Paradoxically, depending on the context, it displays proinflammatory properties by being a potent chemoattractant for neutrophils and promoting inflammation. In addition, it does not only induce differentiation into the anti-inflammatory Treg cells, but also into the proinflammatory Th17 and Th9 cells and inhibits Th22 differentiation. TGF-β has been demonstrated to be involved in multiple pathologies. In infections, it protects against collateral damages caused by the immune system, but it also promotes immune evasion and chronic infections. In autoimmune diseases, a TGF-β dysfunction leads to the loss of tolerance to self-antigens. In cancer, TGF-β is a potent inhibitor of cell proliferation and acts as a tumor suppressor at the beginning of tumorogenesis. However, once the cells become resistant to TGF-β, it mainly supports tumor growth and metastasis by promoting immune evasion and angiogenesis. In asthma, it is assumed to promote allergen tolerance, but plays a detrimental role in irreversible remodeling of the airways. Despite the high numbers of TGF-β-targeted pathways, it is a promising drug target for treatment of autoimmunity, cancer, fibrosis, if cell specificity can be achieved.This review summarizes the progresses that have been accomplished on the understanding of TGF-β's signaling in the immune homeostasis and its role in pathogenesis.
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Anmerkungen
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Herausgeber
Cuturi, M.C.* ; Anegon, I.*
Schlagwörter
TGF-β; SMAD; Immune regulation; Tolerance; Immunopatholgy; T cell differentiation; Th17; Th22; Th9; T regulatory cells; FOXP3; RORγt
Sprache
englisch
Veröffentlichungsjahr
2011
HGF-Berichtsjahr
0
ISSN (print) / ISBN
1064-3745
e-ISSN
1940-6029
Konferenztitel
Suppression and Regulation of Immune Responses : Methods and Protocols
Zeitschrift
Methods in Molecular Biology
Quellenangaben
Band: 677,
Seiten: 303-338
Reihe
Methods Mol. Biol.
Verlag
Springer
Verlagsort
Berlin [u.a.]
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Lung Health and Immunity (LHI)
Institute of Epidemiology (EPI)
Institute of Epidemiology (EPI)
POF Topic(s)
30202 - Environmental Health
PSP-Element(e)
G-521200-001
FE 73991
FE 73991
PubMed ID
20941619
Erfassungsdatum
2011-01-01