IL-2 Family of Cytokines in T Regulatory Cell Development and Homeostasis

Malek, Thomas R.; Yu, Aixin; Zhu, Lin; Matsutani, Takaji; Adeegbe, Dennis O.; Bayer, Allison L.

doi:10.1007/s10875-008-9235-y

Cited by 93 publications

(67 citation statements)

References 40 publications

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“…Furthermore, IL-2 influences cell survival, differentiation [1] and the formation of immune memory cells [1,9] and acts as a negative regulator of immune activation [8]. Recent studies showed that IL-2 played a critical role in the differentiation and survival of regulatory T cells, thereby ensuring their significance in the control of the immune response [10]. Cytokines effectively participate in the pathogenesis of several pathological conditions, such as cancer and metabolic, infectious, autoimmune and inflammatory diseases [11,12].…”

Section: Interleukin 2 and The Immune Responsementioning

confidence: 99%

Human Interleukin 2 (IL-2) Promotion of Immune Regulation and ClinicalOutcomes: A Review

Capobianco¹,

Cassiano²,

Furini³

et al. 2016

J Cytokine Biol

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Interleukin 2 (IL-2) is a monomeric glycoprotein that is primarily produced by activated CD4+ T cells, CD8+ T cells and dendritic cells. It is characterized as a proinflammatory cytokine that is secreted by Th1 cells. IL-2 plays a central role in the activation of regulatory T cells to produce the cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). IL-2 may also enhance the cytolytic activity of natural killer cells, thereby ensuring their significance in the control of the immune response, and effectively participate in the pathogenesis of several pathological conditions, such as cancer and metabolic, infectious, autoimmune and inflammatory diseases. We emphasize the importance of studies of IL-2 and discuss perspectives resulting from our increasing understanding of genetic diversity and its role in the immune response.

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Section: Interleukin 2 and The Immune Responsementioning

confidence: 99%

Human Interleukin 2 (IL-2) Promotion of Immune Regulation and ClinicalOutcomes: A Review

Capobianco¹,

Cassiano²,

Furini³

et al. 2016

J Cytokine Biol

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“…A major role for IL-2 signaling in differentiation of Treg cells is emphasized by diminished numbers of Foxp3 + cells in mice lacking IL-2 or IL-2Ra or IL2Rb chains, the latter shared by IL2 and IL15 receptors. Furthermore, a complete lack of Foxp3 + cells is found in mice lacking common g-chain (gc), a shared signaling subunit of all gc family cytokines, or three key members of the family, IL-2, IL-15, and IL-7 (Fontenot et al 2005b;Burchill et al 2007;Malek et al 2008;Vang et al 2008). Since STAT5 is a key transcription factor activated downstream from gc cytokine signaling, it was proposed that STAT5 plays a pivotal role in induction of Foxp3 expression.…”

Section: Regulation Of Foxp3 Expressionmentioning

confidence: 99%

Molecular orchestration of differentiation and function of regulatory T cells

Lu¹,

Rudensky²

2009

Genes Dev.

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During the last decade, a unique mechanism of negative regulation of immune responses and inflammation by a dedicated population of so-called regulatory T cells (Treg) has become a focus of intensive investigation. Through the discovery of transcription factor Foxp3 as a central molecular determinant of differentiation and function of Treg cells, the complex biology of these cells, including maintenance of immunological tolerance to “self” and regulation of immune responses to pathogens, commensals, and tumors, has become amenable to mechanistic studies. In this review, we discuss the molecular aspects of Treg cell lineage commitment, maintenance, and function.

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“…Treg, making them highly dependent on exogenous IL-2 for their maintenance in the periphery [6, [14][15][16][17]. Deficiency of IL-2, CD25, or CD122 produces fatal autoimmune/inflammatory disease, which is mainly due to defective survival of natural Treg [23]. Yet, it is still conceivable that IL-2 nonproduction by Treg reduces in vitro Treg suppressive activity but, unlike CTLA-4, IL-2, CD25, or CD122 deficiency, fails to breach self-tolerance.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of peripheral tolerance and immune regulation mediated by Treg

2009

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Peripheral self-tolerance and immune homeostasis are maintained, at least in part, by the balance between Treg and effector T cells. Naturally, arising CD25 1 CD41 Treg, which express the transcription factor Foxp3, suppress the activation and proliferation of other lymphocytes in multiple ways. A CTLA-4-dependent suppressive mechanism is shared by every Foxp3 1 Treg at any location and its disruption breaches self-tolerance and immune homeostasis, suggesting that it is a core mechanism of suppression. Depending on the environment, Foxp3 1 Treg also differentiate to exhibit additional suppressive mechanisms, including the secretion of immunosuppressive cytokines. Naïve T cells acquire Foxp3 expression and suppressive activity under certain in vivo and in vitro conditions, whereas some Foxp3 1 T cells may lose Foxp3 and suppressive activity following proliferation in an IL-2-deficient environment. Moreover, activated effector T cells frequently secrete suppressive cytokines, such as IL-10, in a negative feedback fashion. These findings, when taken together, indicate that peripheral immune tolerance and homeostasis are dynamically maintained by functional differentiation within the Foxp3 1 population, occasional conversion between Treg and non-Treg cells, and the interactions among them. These dynamics provide ample opportunities for immune intervention for the benefit of the host.

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IL-2 Family of Cytokines in T Regulatory Cell Development and Homeostasis

Abstract: Thus, IL-2 provides importance signals for Treg cell development and for their homeostasis in peripheral immune tissues.

Cited by 93 publications

References 40 publications

Human Interleukin 2 (IL-2) Promotion of Immune Regulation and ClinicalOutcomes: A Review

Human Interleukin 2 (IL-2) Promotion of Immune Regulation and ClinicalOutcomes: A Review

Molecular orchestration of differentiation and function of regulatory T cells

Dynamics of peripheral tolerance and immune regulation mediated by Treg

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