IL-21 comes of age as a regulator of effector T cells in the gut

Fantini, Massimo; Monteleone, Giovanni; MacDonald, Thomas T.

doi:10.1038/mi.2007.17

Cited by 33 publications

(26 citation statements)

References 50 publications

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“…IL-21 is a pleiotropic cytokine that has both proinflammatory (26) and anti-inflammatory activities (27). It is mainly produced by CD4 + T cells and is critical for CD4-mediated help for B cell and cytotoxic lymphocyte responses (28)(29)(30)(31).…”

Section: Ytokines Regulate the Differentiation Of Uncommitted Naivementioning

confidence: 99%

IL-21 Is a Central Memory T Cell–Associated Cytokine That Inhibits the Generation of Pathogenic Th1/17 Effector Cells

Kastirr

Maglie

Paroni

et al. 2014

The Journal of Immunology

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IL-21 promotes Th17 differentiation, and Th17 cells that upregulate T-bet, IFN-γ, and GM-CSF drive experimental autoimmune diseases in mice. Anti–IL-21 treatment of autoimmune patients is therefore a therapeutic option, but the role of IL-21 in human T cell differentiation is incompletely understood. IL-21 was produced at high levels by human CD4+ central memory T cells, suggesting that it is associated with early T cell differentiation. Consistently, it was inhibited by forced expression of T-bet or RORC2, the lineage-defining transcription factors of Th1 and Th17 effector cells, respectively. Although IL-21 was efficiently induced by IL-12 in naive CD4+ T cells, it inhibited the generation of Th1 effector cells in a negative feedback loop. IL-21 was also induced by IL-6 and promoted Th17 differentiation, but it was not absolutely required. Importantly, however, IL-21 promoted IL-10 secretion but inhibited IFN-γ and GM-CSF production in developing Th17 cells, and consequently prevented the generation of polyfunctional Th1/17 effector cells. Moreover, in Th17 memory cells, IL-21 selectively inhibited T-bet upregulation and GM-CSF production. In summary, IL-21 is a central memory T cell–associated cytokine that promotes Th17 differentiation and IL-10 production, but inhibits the generation of potentially pathogenic Th1/17 effector cells. These findings shed new light on the role of IL-21 in T cell differentiation, and have relevant implications for anti–IL-21 therapy of autoimmune diseases.

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Section: Ytokines Regulate the Differentiation Of Uncommitted Naivementioning

confidence: 99%

IL-21 Is a Central Memory T Cell–Associated Cytokine That Inhibits the Generation of Pathogenic Th1/17 Effector Cells

Kastirr

Maglie

Paroni

et al. 2014

The Journal of Immunology

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“…IL-21 is an important regulator of T cell expansion, differentiation and effector function [60,61]. In mouse and humans, IL-21 enhances anti-CD3 induced proliferation of T cells, and can act in concert with other type I cytokines to further enhance the growth of CD4 T cells.…”

Section: Enhancement Of T Cell Differentiation Proliferation and Effmentioning

confidence: 99%

Role of IL-21 in Systemic Lupus Erythematosus

Jung¹,

Guay²

2011

J Clin Cell Immunol

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Systemic lupus erythematosus is a chronic autoimmune disease that affects multiple organ systems and tissues. Activation and differentiation of autoreactive T and B cells, and the formation of pathogenic autoantibodies are central to disease pathogenesis. IL-21 is the most recently identified member of the family of cytokines whose receptors share the common γ c . IL-21 is a pleotropic cytokine that regulates the activation, differentiation and expansion of B and T cells. Here, we review the role of IL-21 in T and B cell biology, and provide insight into the potential role of IL-21 in the development of SLE.

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“…Nevertheless, IL-21 could also trigger inflammatory pathways that promote tissue damage in various organs. 12,13 Hence, it is possible that IL-21 exerts effects on inflammatory responses in the liver that promote the development of inflammatory disorders. Here, we review the current knowledge on the immunomodulatory effects of IL-21 in HBV infection.…”

Section: Introductionmentioning

confidence: 99%