Ex Vivo IL-1 Receptor Type I Expression in Human CD4+ T Cells Identifies an Early Intermediate in the Differentiation of Th17 from FOXP3+ Naive Regulatory T Cells

Raffin, Caroline; Raimbaud, Isabelle; Valmori, Danila; Ayyoub, Maha

doi:10.4049/jimmunol.1101742

Cited by 30 publications

(29 citation statements)

References 27 publications

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“…The same upregulation of IL-1RI was described by Raffin and colleagues (47) on PB naïve CD4+ T cell in the presence of the combination of IL-2, IL-1β, IL-23, and TGF-β.…”

Section: Both Mice and Humans Th17 Express Il-1ri And Are Modulated Bsupporting

confidence: 78%

IL-1 and T Helper Immune Responses

Santarlasci¹,

Cosmi²,

Maggi³

et al. 2013

Front. Immunol.

122

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CD4 T cells play a critical role in mediating adaptive immunity to a variety of pathogens as well as in tumor immunity. If not adequately regulated, CD4 T cells can be also involved in autoimmunity, asthma, and allergic responses. During TCR activation in a particular cytokine milieu, naïve CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, and Th17, as defined by their pattern of cytokine production and function. IL-1, the prototypic proinflammatory cytokine, has been shown to influence growth and differentiation of immunocompetent lymphocytes. The differential expression of IL-1RI on human CD4 T cell subsets confers distinct capacities to acquire specific effector functions. In this review, we summarize the role of IL-1 on CD4 T cells, in terms of differentiation, activation, and maintenance or survival.

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“…The same upregulation of IL-1RI was described by Raffin and colleagues (47) on PB naïve CD4+ T cell in the presence of the combination of IL-2, IL-1β, IL-23, and TGF-β.…”

Section: Both Mice and Humans Th17 Express Il-1ri And Are Modulated Bsupporting

confidence: 78%

IL-1 and T Helper Immune Responses

Santarlasci¹,

Cosmi²,

Maggi³

et al. 2013

Front. Immunol.

122

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“…Of particular interest are the data we obtained concerning Tregs express Aiolos, together with RORgt and C-MAF, which respectively direct IL-17 and IL-10 production, support the concept that they encompass iTregs that differentiate along a pathway partially common to T H 17 cells (11). Another significant finding was that Helios 2 Tregs, which secrete IL-17, were highly suppressive ex vivo.…”

Section: Discussionsupporting

confidence: 53%

Human Memory Helios− FOXP3+ Regulatory T Cells (Tregs) Encompass Induced Tregs That Express Aiolos and Respond to IL-1β by Downregulating Their Suppressor Functions

Raffin

Pignon

Celse

et al. 2013

The Journal of Immunology

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FOXP3+ regulatory T cells (Tregs) are critical regulators of self-tolerance and immune homeostasis. In mice and humans, two subsets of FOXP3+ Tregs have been defined based on their differential expression of Helios, a transcription factor of the Ikaros family. Whereas the origin, specificity, and differential function of the two subsets are as yet a source of controversy, their characterization thus far has been limited by the absence of surface markers to distinguish them. In this article, we show that human memory Helios+ and Helios− Tregs are phenotypically distinct and can be separated ex vivo based on their differential expression of IL-1RI, which is restricted to Helios− Tregs, in combination with CCR7. The two populations isolated using this strategy are distinct with respect to the expression of other Ikaros family members. Namely, whereas Eos, which has been reported to mediate FOXP3-dependent gene silencing, is expressed in Helios+ Tregs, Aiolos, which is involved in the differentiation of TH17 and induced Tregs, is instead expressed in Helios− Tregs. In addition, whereas both subsets are suppressive ex vivo, Helios− Tregs display increased suppressive capacity in comparison to Helios+ Tregs, but respond to IL-1β by downregulating their suppressive activity. Together, these data support the concept that human Helios− memory Tregs encompass induced Tregs that can readily respond to changes in the environment by modulating their suppressive capacity.

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“…We first assessed the previously reported IL-1R1 and CD161 as potential markers for IL-17+Treg precursors (36-38). While sorting cells based on these markers did enhance IL-17-secreting-cell differentiation (Fig.…”

Section: Resultsmentioning

confidence: 99%

Differentiation of IL-17–Producing Effector and Regulatory Human T Cells from Lineage-Committed Naive Precursors

Mercer

Khaitan

Kozhaya

et al. 2014

The Journal of Immunology

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A subset of human regulatory T cells (Tregs) secretes IL-17 and thus resembles Th17 effector cells. How IL-17+Treg cells differentiate from naïve precursors remains unclear. Here, we show that IL-17-producing T-cells can differentiate from CCR6+ naïve T cell precursors in the presence of IL-2, IL-1β, TGF-β, and IL-23. CCR6+ naïve T cells are present in adult peripheral and umbilical cord blood and in both conventional T naïve (TN) and FOXP3+ naïve Treg (TNreg) subsets. IL-17+ cells derived from CCR6+ TNreg cells (referred to as IL-17+Treg) express FOXP3, but not HELIOS, another Treg-associated transcription factor, and these cells display suppressor capacity and a surface phenotype resembling memory Tregs. Remarkably, the IL-17+Treg compartment was preferentially reduced relative to the canonical Th17 and Treg compartments in a subset of HIV+ subjects, suggesting a specific perturbation of this subset during the course of disease. Our findings that CCR6+ naïve precursors contain a predetermined reservoir to replenish IL-17-secreting cells, may have implications in balancing the Th17 and IL-17+Treg compartments that are perturbed during HIV infection and potentially in other inflammatory diseases.

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Ex Vivo IL-1 Receptor Type I Expression in Human CD4+ T Cells Identifies an Early Intermediate in the Differentiation of Th17 from FOXP3+ Naive Regulatory T Cells

Cited by 30 publications

References 27 publications

IL-1 and T Helper Immune Responses

IL-1 and T Helper Immune Responses

Human Memory Helios− FOXP3+ Regulatory T Cells (Tregs) Encompass Induced Tregs That Express Aiolos and Respond to IL-1β by Downregulating Their Suppressor Functions

Differentiation of IL-17–Producing Effector and Regulatory Human T Cells from Lineage-Committed Naive Precursors

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