IL-9 induces differentiation of T
            <sub>H</sub>
            17 cells and enhances function of FoxP3
            <sup>+</sup>
            natural regulatory T cells

Elyaman, Wassim; Bradshaw, Elizabeth M.; Uyttenhove, Catherine; Dardalhon, Valérie; Awasthi, Amit; Imitola, Jaime; Bettelli, Estelle; Oukka, Mohamed; Snick, Jacques Van; Renauld, Jean‐Christophe; Kuchroo, Vijay K.; Khoury, Samia J.

doi:10.1073/pnas.0812530106

Cited by 437 publications

(428 citation statements)

References 35 publications

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“…Moreover, it has also been shown that IL-9 synergizes with TGF-beta1 to differentiate naive CD4 + T cells into Th17 cells and postulated an additional role for IL-9 in mediating the suppressive function of Tregs in experimental autoimmune encephalomyelitis. 38 Thus, our microarray data are coherent with these findings and provide further support for the importance of IL-27 and IL-9 cytokine signalling in the development of T1D.…”

Section: Discussionsupporting

confidence: 84%

Case report: type 1 diabetes in monozygotic quadruplets

et al. 2011

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Type 1 diabetes (T1D) is an autoimmune disease characterized by the lack of insulin due to an autoimmune destruction of pancreatic beta cells. Here, we report a unique case of a family with naturally conceived quadruplets in which T1D was diagnosed in two quadruplets simultaneously. At the same time, the third quadruplet was diagnosed with the pre-diabetic stage. Remarkably, all four quadruplets were positive for anti-islet cell antibodies, GAD65 and IA-A2. Monozygotic status of the quadruplets was confirmed by testing 14 different short tandem repeat polymorphisms. Serological examination confirmed that all quadruplets and their father suffered from a recent enteroviral infection of EV68-71 serotype. To assess the nature of the molecular pathological processes contributing to the development of diabetes, immunocompetent cells isolated from all family members were characterized by gene expression arrays, immune-cell enumerations and cytokine-production assays. The microarray data provided evidence that viral infection, and IL-27 and IL-9 cytokine signalling contributed to the onset of T1D in two of the quadruplets. The propensity of stimulated immunocompetent cells from non-diabetic members of the family to secrete high level of IFN-a further corroborates this conclusion. The number of T regulatory cells as well as plasmacytoid and/or myeloid dendritic cells was found diminished in all family members. Thus, this unique family is a prime example for the support of the so-called 'fertile-field' hypothesis proposing that genetic predisposition to anti-islet autoimmunity is 'fertilized' and precipitated by a viral infection leading to a fully blown T1D.

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Section: Discussionsupporting

confidence: 84%

Case report: type 1 diabetes in monozygotic quadruplets

et al. 2011

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“…These results changed our perception of the IL-9 stimulating activity of TGF-b/IL-4 reported by Schmitt [11]. More recently, still, IL-9 production by CD4 1 T cells stimulated in the presence of TGF-b/IL-6, the canonical Th17 combination [12][13][14], was also reported [15,16].…”

Section: Introductionmentioning

confidence: 58%

“…Several publications have reported IL-9 production by purified Th17 CD4 1 T cells activated with anti-CD3/CD28 [15,16]. We carefully tested this condition in antigen recall responses of mice immunized with OVA.…”

Section: Introductionmentioning

confidence: 99%

TGF‐β interactions with IL‐1 family members trigger IL‐4‐independent IL‐9 production by mouse CD4⁺ T cells

2010

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TGF-b and IL-4 were recently shown to selectively upregulate IL-9 production by naïve CD4 1 T cells. We report here that TGF-b interactions with IL-1a, IL-1b, IL-18, and IL-33 have equivalent IL-9-stimulating activities that function even in IL-4-deficient animals. This was observed after in vitro antigenic stimulation of immunized or unprimed mice and after polyclonal T-cell activation. Based on intracellular IL-9 staining, all IL-9-producing cells were CD4 1 and 80-90% had proliferated, as indicated by reduced CFSE staining. In contrast to IL-9, IL-13 and IL-17 were strongly stimulated by IL-1 and either inhibited (IL-13) or were unaffected (IL-17) by addition of TGF-b. IL-9 and IL-17 production also differed in their dependence on IL-2 and regulation by IL-1/IL-23. As IL-9 levels were much lower in Th2 and Th17 cultures, our results identify TGF-b/IL-1 and TGF-b/IL-4 as the main control points of IL-9 synthesis.

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“…However, the net effect of IL-9 depends on the cellular context. There are hints that IL-9 may act directly on Tregs (which express IL-9Ra), enhancing their suppressive function and indirectly on Th17 cells (which do not express IL-9Ra), promoting their proliferation and/or accumulation [98]. IL-9 induces the expression of the chemokine CCL20 by astrocytes, which enhances the migration of Th17 cells into the CNS.…”

Section: Il-9mentioning

confidence: 99%

Cytokines and effector T cell subsets causing autoimmune CNS disease

2011

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a b s t r a c tAlthough experimental autoimmune encephalomyelitis (EAE) is limited in its potency to reproduce the entirety of clinical and histopathologic features of multiple sclerosis (MS), this model has been successfully used to prove that MS like autoimmunity in the CNS is orchestrated by autoantigen specific T cells. EAE was also very useful to refute the idea that IFN-c producing T helper type 1 (Th1) cells were the sole players within the pathogenic T cell response. Rather, ''new'' T cell lineages such as IL-17 producing Th17 cells or IL-9 producing Th9 cells have been first discovered in the context of EAE. Here, we will summarize new concepts of early and late T cell plasticity and the cytokine network that shapes T helper cell responses and lesion development in CNS specific autoimmunity.

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IL-9 induces differentiation of T _H 17 cells and enhances function of FoxP3 ⁺ natural regulatory T cells

Abstract: The development of T helper (TH)17 and regulatory T (Treg

Cited by 437 publications

References 35 publications

Case report: type 1 diabetes in monozygotic quadruplets

Case report: type 1 diabetes in monozygotic quadruplets

TGF‐β interactions with IL‐1 family members trigger IL‐4‐independent IL‐9 production by mouse CD4⁺ T cells

Cytokines and effector T cell subsets causing autoimmune CNS disease

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IL-9 induces differentiation of T H 17 cells and enhances function of FoxP3 + natural regulatory T cells

Abstract: The development of T helper (TH)17 and regulatory T (Treg

Cited by 437 publications

References 35 publications

Case report: type 1 diabetes in monozygotic quadruplets

Case report: type 1 diabetes in monozygotic quadruplets

TGF‐β interactions with IL‐1 family members trigger IL‐4‐independent IL‐9 production by mouse CD4+ T cells

Cytokines and effector T cell subsets causing autoimmune CNS disease

Contact Info

Product

Resources

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IL-9 induces differentiation of T _H 17 cells and enhances function of FoxP3 ⁺ natural regulatory T cells

TGF‐β interactions with IL‐1 family members trigger IL‐4‐independent IL‐9 production by mouse CD4⁺ T cells