Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cells

Batten, Marcel; Li, J i; Yi, Sothy; Kljavin, Noelyn M.; Danilenko, Dimitry M.; Lucas, Sophie; Lee, James; Sauvage, Frédéric J. de; Ghilardi, Nico

doi:10.1038/ni1375

Cited by 757 publications

(809 citation statements)

References 44 publications

Supporting

Mentioning

754

Contrasting

Unclassified

Order By: Relevance

“…9A and B). Consistent with these data, Ghilardi and colleagues [22] reported that IL-27 specifically suppressed IL-6-induced proliferation of CD4 + CD25 -effector but not regulatory T cells. Thus, the enhanced IL-17 expression in EBI3 -/-mice is unlikely due to an inhibition of the population of Foxp3 + CD25 + regulatory T cells.…”

Section: Ebi3 -/-Mice Are Resistant To L Monocytogenes Infectionmentioning

confidence: 54%

“…IL-27Ra-deficient mice studies indicate that IL-27 negatively regulates the development of Th17 cells [22,23]. However, there is no IL-27 (EBI3 or p28) deficiency study to directly prove the role of IL-27 on the regulation of IL-17 and Th17 cells.…”

Section: Resultsmentioning

confidence: 99%

“…They also found that the p28 subunit of IL-27 alone suppressed IL-17 production, although not as efficiently as IL-27 [23]. Batten and colleagues [22] discovered that IL-27Ra-deficient mice exhibited increased susceptibility to EAE and generated more IL-17-producing T cells than WT mice. In addition, they found that IL-27 in vitro acted directly on effector T cells to suppress the development of IL-17-producing T helper cells driven by IL-6 and TGF-b.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies using mouse models have shown that the function(s) of IL-27 are broader and more complex, and a role for IL-27 as a positive as well as a negative regulator of T cell responses has emerged. Recent studies using IL-27Ra-deficient mice indicate that IL-27 negatively regulates the development of Th17 cells [22,23]. Liew and colleagues [15] recently demonstrated that IL-35 inhibits Th17 cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Epstein‐Barr virus‐induced gene 3 negatively regulates IL‐17, IL‐22 and RORγt

Yang

Htut

et al. 2008

Eur J Immunol

View full text Add to dashboard Cite

Epstein-Barr virus-induced gene 3 (EBI3) associates with p28 to form IL-27 and with IL-12p35 to form IL-35. IL-27Ra -/-mice studies indicate that IL-27 negatively regulates Th17 cell differentiation. However, no EBI3, p28 or p35-deficiency studies that directly address the role of EBI3, p28 or p35 on Th17 cells have been done. Here, we demonstrate that spleen cells derived from EBI3 -/-mice produce significantly higher levels of IL-17 as well as IL-22 upon stimulation with OVA. In vitro derived EBI3 -/-Th17 cells also produced significantly higher levels of IL-17 and IL-22 than WT cells. The frequency of IL-17-producing cells was also elevated when EBI3 -/-cells were cultured under Th17 conditions. In addition, spleen cells from EBI3 -/-mice immunized with Listeria monocytogenes produced significantly elevated levels of IL-17 and IL-22. Furthermore, the Th17 transcription factor RORct was significantly enhanced in EBI3 -/-cells. Finally, EBI3 -/-mice exhibited a reduced bacterial load following an acute challenge with L. monocytogenes or a re-challenge of previously immunized mice, suggesting that EBI3 negatively regulates both innate and adaptive immunity. Taken together, these data provide direct evidence that EBI3 negatively regulates the expression of IL-17, IL-22 and RORct as well as protective immunity against L. monocytogenes.

show abstract

Section: Ebi3 -/-Mice Are Resistant To L Monocytogenes Infectionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Epstein‐Barr virus‐induced gene 3 negatively regulates IL‐17, IL‐22 and RORγt

Yang

Htut

et al. 2008

Eur J Immunol

View full text Add to dashboard Cite

show abstract

“…42,44,114,129 The anti-inflammatory effects of IL-27 are highlighted by the development of exaggerated Th17 immunity and severe EAE by IL-27 receptor alpha (IL-27Ra)-deficient mice. 130 IL-27 is produced by innate cells in response to TLR activation, by a mechanism that involves the autocrine effects of IFN-b. 131,132 As exogenous IFN-b triggers IL-27 production by cells of the innate immune system including DCs, 133 it has been proposed that the beneficial effects of IFN-b treatment in RRMS involve the induction of IL-27 synthesis and its effects on Tr1 and Th17 cell differentiation.…”

Section: Regulation Of DC Function By Il-27mentioning

confidence: 99%

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

2014

View full text Add to dashboard Cite

Dendritic cells (DCs) are professional antigen-presenting cells that control the generation of adaptive immunity. Consequently, DCs have a central role in the induction of protective immunity to pathogens and also in the pathogenic immune response responsible for the development and progression of autoimmune disorders. Thus the study of the molecular pathways that control DC development and function is likely to result in new strategies for the therapeutic manipulation of the immune response. In this review, we discuss the role and therapeutic value of DCs in autoimmune diseases, with a special focus on multiple sclerosis. Cell Death and Differentiation (2015) 22, 215-224; doi:10.1038/cdd.2014; published online 29 August 2014 FactsDendritic cells (DCs) control central and peripheral tolerance through their effects on effector and regulatory T cells. Specific signaling pathways regulate the ability of different DC populations to promote effector and regulatory T-cell responses. Abnormalities in DC numbers, recruitment and function contribute to the pathology of multiple sclerosis (MS) and can be partially overcome by the use of disease-modifying therapies and the targeting of specific molecular pathways. Nanotechnology provides new tools for the modulation of DC activity in vivo and the therapeutic induction of antigenspecific tolerance in immune-mediated disorders. Open QuestionsAlthough DC populations that promote the development of forkhead box P3-positive (FoxP3 þ ) regulatory T cells (Tregs) have been identified, it is not yet clear whether these populations constitute separate tolerogenic DC lineages or represent alternative activation or maturation states of other DC populations. What are the different molecular pathways that control the DC's ability to prime effector or tolerogenic T-cell responses?There is an unmet clinical need for the development of methods for the efficient and consistent generation of tolerogenic DCs in vitro and in vivo that can be implemented in large-scale clinical setups.Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that control the activation and polarization of T cells into specific lineages and, consequently, the generation of antigen-specific antibody and T-cell responses. 1 In the context of an infectious challenge, the induction of pathogenspecific immune responses provides protective immunity to fight the infection. However, in the context of autoimmune diseases DCs regulate the balance between pathogenic and regulatory immune mechanisms, controlling disease onset and progression. Thus, DCs have a central role in the control of the adaptive immune response to pathogens and selftissues and therefore constitute potential targets for the therapeutic modulation of the immune response. In this review, we discus the role of DCs in autoimmune diseases, with a special emphasis on their role in the modulation of central nervous system (CNS) inflammation in MS. Received 12.6.14; accepted 23.6.14; Edited by H-U Simon; published online 29.8.14 Abbreviations: A...

show abstract

Interleukins

Meager

Wadhwa

2007

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

The interleukins (IL) belong to a category of biologically active proteins, termed cytokines. These proteins are derived mainly from white blood cells and act on white cells, although these criteria are not necessarily exclusive of other cell sources and activities. Interleukins, among other proteins, maintain the haematopoietic and immune systems and control their functions. They have been classified specifically by a designated nomenclature committee of the International Union of Immunological Societies/World Health Organization. In general, numbering of interleukins has followed the order of their discovery and this has led to some anomalies. It has become evident that interleukins can be classified into subgroups or families based on shared structural characteristics, and/ or shared receptor subunits and/or shared chromosomal locations. For example, IL‐1α, IL‐1β, IL‐18 and IL‐33 belong to the ‘IL‐1 family’, IL‐2, IL‐15 and IL‐21 to the ‘IL‐2 family’ (IL‐4, IL‐7, IL‐9 and IL‐13 might also be included as they share at least one receptor subunit with IL‐2 family members), IL‐10, IL‐19, IL‐20, IL‐22, IL‐24, IL‐26, IL‐28 and IL‐29 to the ‘IL‐10 family’, IL‐12, IL‐23 and IL‐27 to the ‘IL‐12 family’. IL‐3 and IL‐5 together with GM‐CSF and IL‐6 and IL‐11 together with several other noninterleukin named cytokines – LIF, OSM, CNTF, CT‐1 – can also be grouped as families of ‘like’ cytokines. The IL‐17 family is comprised of six related proteins (IL‐17A–F), one of which, the murine homologue of IL‐17E, was anomalously designated IL‐25. With hindsight, the remaining interleukins might have been better classified with other biological modifiers. For instance, IL‐8 is clearly a chemokine; IL‐14 and IL‐16 bear scant resemblance to any other interleukins, or other cytokines for that matter. In the following paper, the molecular characteristics of interleukin proteins, their cognate receptors and intracellular signalling pathways and their biological activities are briefly described. The interactions of particular interleukins in the regulation of immune cell growth, differentiation and function will be illustrated by short sections at the end of the paper covering (1) T‐lymphocyte development and activation and (2) chronic inflammation and autoimmunity.

show abstract

Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17–producing T cells

Cited by 757 publications

References 44 publications

Epstein‐Barr virus‐induced gene 3 negatively regulates IL‐17, IL‐22 and RORγt

Epstein‐Barr virus‐induced gene 3 negatively regulates IL‐17, IL‐22 and RORγt

Role and therapeutic value of dendritic cells in central nervous system autoimmunity

Interleukins

Contact Info

Product

Resources

About