REGULATION OF IMMUNE RESPONSES BY TGF-β*

By J. Letterio, A. Roberts. 1998

The transforming growth factor beta (TGF-beta) family of proteins are a set of pleiotropic secreted signaling molecules with unique and potent immunoregulatory properties. TGF-beta 1 is produced by every leukocyte lineage, including lymphocytes, macrophages, and dendritic cells, and its expression serves in both autocrine and paracrine modes to control the differentiation, proliferation, and state of activation of these immune cells. TGF-beta can modulate expression of adhesion molecules, provide a chemotactic gradient for leukocytes and other cells participating in an inflammatory response, and inhibit them once they have become activated. Increased production and activation of latent TGF-beta have been linked to immune defects associated with malignancy and autoimmune disorders, to susceptibility to opportunistic infection, and to the fibrotic complications associated with chronic inflammatory conditions. In addition to these roles in disease pathogenesis, TGF-beta is now established as a principal mediator of oral tolerance and can be recognized as the sine qua non of a unique subset of effector cells that are induced in this process. The accumulated knowledge gained through extensive in vitro functional analyses and from in vivo animal models, including newly established TGF-beta gene knockout and transgenic mice, supports the concept that clinical therapies based on modulation of this cytokine represent an important new approach to the treatment of disorders of immune function.

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

1. J. Massagué
2. J. Seoane
3. R. Derynck
4. M. Dobaczewski
5. A. Biernacka
6. R. Akhurst
7. M. Nieto
8. D. Wotton

Citations in the corpus

• Smad transcription factors. (2005, methodology): “For more information on the biology of the TGF family, we would recommend several classical reviews (Letterio and Roberts 1998; Whitman 1998; Massagué and Chen 2000; Massagué et al. 2000; Derynck et al. 2001; Attisano and Wrana 2002; Schier 2003).”
• Fibrotic disease and the TH1/TH2 paradigm (2004, background): “, another potent pro-fibrotic cytokine that has been widely studie”
• Diverse Roles of TGF-β/Smads in Renal Fibrosis and Inflammation (2011, unknown): “kines [13].”
• Mechanisms of immune evasion by tumors. (2006, background): “From an immunological perspective, TGF‐b possesses broadly immunosuppressive properties and TGF‐b knockout mice develop widespread inflammatory pathology and corresponding accelerated mortality (Letterio and Roberts, 1998).”
• TGF-β signaling in tumor suppression and cancer progression (2001, background): “TGF-β inhibits the proliferation and functional differentiation of T lymphocytes, lymphokine-activated killer cells, NK cells, neutrophils, macrophages and B cell”
• The role of TGF-β Signaling in Myocardial Infarction and Cardiac Remodeling (2007, background): “The cellular actions of TGF-β are not only dependentonthecelltypebutalsoonitsstateofdifferentiation and on the cytokine milieu [ 2 ].”
• Transforming Growth Factor (TGF)-β signaling in cardiac remodeling (2010, background): “Femtomolar concentrations of TGF-β induce monocyte chemotaxis [28]; picomolar concentrations activate monocytes, stimulating synthesis of cytokines, chemokines and growth factors [19,28] and increasing integrin expression.”