Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis

Chen, Yi; Langrish, Claire L.; McKenzie, Brent; Joyce-Shaikh, Barbara; Stumhofer, Jason S.; McClanahan, Terrill K.; Blumenschein, Wendy M.; Churakovsa, Tatyana; Low, Justin; Presta, Leonard G.; Hunter, Christopher A.; Kastelein, Robert A.; Daniel, J.

doi:10.1172/jci25308

Cited by 519 publications

(421 citation statements)

References 57 publications

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“…IL-23 has been reported to be essential for the development of autoimmunity in mouse models, and current data suggest that this is due to the production of IL-17 (6,(8)(9)(10)26,39). We found that naive CD4ϩ T cells expressed low levels of IL-23R mRNA compared with memory CD4ϩ T cells (Figure 4a).…”

Section: Il-23 Up-regulation Of Il-23r and Enhancement Of Il-17 Produmentioning

confidence: 50%

“…The current view of mouse Th17 development is that TGF␤1 and IL-6 are the key cytokines that initiate the differentiation process and that IL-23 plays an essential role in the expansion and maintenance of this lineage. Support for the notion of an IL-23/IL-17 axis has been provided by a number of models of autoimmunity (6,(8)(9)(10)(11)26,39,(44)(45)(46), but despite these compelling data in mice, a systematic analysis of human Th17 differentiation from naive cells has not yet been undertaken.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have supported the notion of a role of IL-23 in autoimmune responses, and a preponderance of evidence indicates that this cytokine may be more clinically relevant than its close relative IL-12 in causing autoimmunity (8)(9)(10)(11)45). The recent discovery of the relationship between IL-23R single-nucleotide polymorphisms and the prevalence of inflammatory bowel disease highlights the relevance of this cytokine in human autoimmune disease (48).…”

Section: Il-17 Regulation In Human T Cellsmentioning

confidence: 95%

“…Similarly, anti-p40 antibody is efficacious in the treatment of Crohn's disease (7). Although these effects were initially misattributed to interference with the actions of IL-12, using specific deletion of IL-23 (p19 Ϫ/Ϫ mice), it is now recognized that IL-23 (and not IL-12) is the culprit, at least in many of the animal models (8)(9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Distinct regulation of interleukin‐17 in human T helper lymphocytes

Chen¹,

Tato²,

Muul³

et al. 2007

Arthritis & Rheumatism

318

281

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Section: Il-23 Up-regulation Of Il-23r and Enhancement Of Il-17 Produmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Il-17 Regulation In Human T Cellsmentioning

confidence: 95%

mentioning

confidence: 99%

See 2 more Smart Citations

Distinct regulation of interleukin‐17 in human T helper lymphocytes

Chen¹,

Tato²,

Muul³

et al. 2007

Arthritis & Rheumatism

318

281

View full text Add to dashboard Cite

“…TIM-3 expression has been reported on mouse Th17 cells [34], DC, monocytes, macrophages [35] and on human NK and NK-T cells [36], indicating that TIM-3 may have different functions in adaptive and innate immunity. Interestingly, the gal-9-TIM-3 pathway showed a stimulatory function in DC, with an enhanced inflammatory response by TIM-3-expressing DC during the innate immune response [37].…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Th1 response through galectin‐9 and T‐cell Ig mucin 3 interaction inhibits autoimmune diabetes in NOD mice

2009

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Galectin-9 (gal-9), widely expressed in many tissues, regulates Th1 cells and induces their apoptosis through its receptor, T-cell Ig mucin 3, which is mainly expressed on terminally differentiated Th1 cells. Type 1 diabetes is a Th1-dominant autoimmune disease that specifically destroys insulin-producing b cells. To suppress the Th1 immune response in the development of autoimmune diabetes, we overexpressed gal-9 in NOD mice by injection of a plasmid encoding gal-9. Mice treated with gal-9 plasmid were significantly protected from diabetes and showed less severe insulitis compared with controls. Flow cytometric analyses in NOD-T1/2 double transgenic mice showed that Th1-cell population in spleen, pancreatic lymph node and pancreas was markedly decreased in gal-9 plasmidtreated mice, indicating a negative regulatory role of gal-9 in the development of pathogenic Th1 cells. Splenocytes from gal-9 plasmid-treated mice were less responsive to mitogenic stimulation than splenocytes from the control group. However, adoptive transfer of splenocytes from gal-9-treated or control mice caused diabetes in NOD/SCID recipients with similar kinetics, suggesting that gal-9 treatment does not induce active tolerance in NOD mice. We conclude that gal-9 may downregulate Th1 immune response in NOD mice and could be used as a therapeutic target in autoimmune diabetes.Key words: Galectin-9 . Th1 . T-cell Ig mucin 3 . Type 1 diabetes IntroductionWhen CD4 1 Th cells interact with class II MHC-peptide complex and costimulatory molecules on APC, they differentiate into several effector subsets. There are two major Th subsets that have unique patterns of cytokine secretion and different functional properties. Th1 cells produce cytokines such as IFN-g, IL-2, TNF-a and lymphotoxin that are commonly associated with cellmediated immune responses against intracellular pathogens, delayed-type hypersensitivity and induction of organ-specific autoimmune diseases. Th2 cells produce cytokines such as IL-4, IL-5, IL-10 and IL-13 that are crucial for controlling extracellular helminth infections and promoting atopic and allergic diseases [1,2].Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease that selectively destroys the insulin-producing b cells in the pancreas. NOD mice spontaneously develop autoimmune diabetes with immunopathological features resembling those of human disease and can be used as an animal model to study the pathogenesis of T1D. Previous studies have demonstrated that transfer of NOD CD4 1 T cells to immunodeficient NOD/SCID mice can induce diabetes in those recipients, indicating that CD4 1 T cells play an important role in the pathogenesis of diabetes [3,4] [12]. Previous approaches using TIM-3-Ig fusion protein to interrupt the interactions between TIM-3 and its ligand in vivo resulted in hyperproliferation of Th1 cells and release of Th1-related cytokines [13]. TIM-3 ligand was subsequently identified as galectin-9 (gal-9) [14], a b-galactoside binding lectin that belongs to a growing family of animal lectins, the...

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Consensus Guidelines for the Management of Plaque Psoriasis

et al. 2012

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he Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

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Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis

Cited by 519 publications

References 57 publications

Distinct regulation of interleukin‐17 in human T helper lymphocytes

Distinct regulation of interleukin‐17 in human T helper lymphocytes

Attenuation of Th1 response through galectin‐9 and T‐cell Ig mucin 3 interaction inhibits autoimmune diabetes in NOD mice

Consensus Guidelines for the Management of Plaque Psoriasis

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