Anti-inflammatory and pro-inflammatory roles of TGF-β, IL-10, and IL-22 in immunity and autoimmunity

doi:10.1016/j.coph.2009.04.008

Current Opinion in Pharmacology

Volume 9, Issue 4, August 2009, Pages 447-453

https://doi.org/10.1016/j.coph.2009.04.008 Get rights and content

Cytokines play a major role in maintaining lymphocyte homeostasis under both steady-state and inflammatory conditions. Unregulated lymphocytes in steady-state conditions can lead to autoimmunity, whereas during inflammation they can cause excessive tissue damage. Regulatory cytokines function in combination with other environmental signals to properly modulate the function and the extent of lymphocyte activation. Many recent studies have highlighted the importance of regulatory cytokines in controlling the differentiation and function of lymphocytes under steady-state and inflammatory conditions, as well as minimizing tissue damage.

Section snippets

TGF-β

Transforming growth factor β (TGF-β) is a pleiotropic cytokine with potent regulatory and inflammatory activity [1••, 2]. The multi-faceted effects of TGF-β on numerous immune functions are cellular and environmental context dependent [3]. TGF-β binds to TGF-β receptor II (TGF-βRII) triggering the kinase activity of the cytoplasmic domain that in turn activates TGF-βRI. The activated receptor complex leads to nuclear translocation of Smad molecules, and transcription of target genes [3]. The

IL-10

IL-10 is a key regulator of the immune system by limiting the inflammatory response that could otherwise cause tissue damage. In addition, IL-10 is essential for homeostasis of the immune system; especially in the gastrointestinal tract. Mice deficient in IL-10 signaling are highly susceptible to colitis owing to aberrant immune responses to commensal bacteria; this colitis is more severe when combined with deficiency in TGF-β signaling [25, 26]. During acute infections, blocking IL-10

IL-22

Interleukin-22 (IL-22) is a member of the IL-10 related cytokine family, which also includes IL-19, IL-20, IL-24 and IL-26 [42, 43, 44]. The IL-22 receptor is highly expressed within tissues, such as epithelial cells of the gastrointestinal tract and skin [45, 46•]. IL-22 signals through a heterodimer comprising IL-22R and IL-10Rβ [47]. Similar to IL-10, IL-22 activates Stat3 signaling pathways in target cells. IL-22 signaling leads to activation of proliferative and/or anti-apoptotic programs,

Concluding remarks

Under steady-state conditions, TGF-β signaling in lymphocytes assures that these cells do not become activated in response to self-antigens (Figure 1a), while IL-10 producing T cells in the gut maintain tolerance against commensal bacteria and food antigens (Figure 1b). Under inflammatory conditions, activation of DCs by PAMPs leads to the production of IL-10 that dampens the immune response of lymphocytes to pathogenic infections, minimizing damage to the host. Meanwhile, in combination with

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

The authors would like to apologize for omitting the citation of many important and significant primary articles, as they were limited by number of citations. RAF is an investigator of the Howard Hughes Medical Institute. This work is supported by post-doctoral fellowship grants from the Cancer Research Institute (SS), the American Liver Foundation and the American Cancer Society (LAZ), with additional support from NIH grants CA121974, DK051665, and P01AI36529 (RAF), JDRF grant 32-2008-352

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Anti-inflammatory and pro-inflammatory roles of TGF-β, IL-10, and IL-22 in immunity and autoimmunity

Section snippets

TGF-β

IL-10

IL-22

Concluding remarks

References and recommended reading

Acknowledgements

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