Hematopoietic prostaglandin D synthase defines a proeosinophilic pathogenic effector human TH2 cell subpopulation with enhanced function

Mitson-Salazar, Alyssa; Yin, Yuzhi; Wansley, Daniel; Young, Michael L.; Bolan, Hyejeong; Arceo, Sarah; Ho, Nancy T.; Koh, Christopher; Milner, Joshua D.; Stone, Kelly D.; Wank, Stephen A.; Prussin, Calman

doi:10.1016/j.jaci.2015.08.007

Cited by 142 publications

(175 citation statements)

References 52 publications

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“…Consistently, elevated numbers of CD3 + , CD4 + , and CD8 + T cells have been reported in the esophageal tissue of patients with EoE. Furthermore, increased numbers of activated CD3 + esophageal T cells [42] and a specific subset of CRTH2 + , PGD2-expressing memory effector Th2 cells that express IL-5 and IL-13 are detected [43 •• ]. Animal models of EoE recapitulate the observation of increased numbers of activated T cells in the esophagus [44], and experimental EoE is T cell dependent and to a lesser extent CD4 + T cell dependent [45].…”

Section: Development Of the Type 2 Inflammatory Milieu In Eoementioning

confidence: 60%

Novel immunologic mechanisms in eosinophilic esophagitis

Caldwell

Paul

Rothenberg

2017

Current Opinion in Immunology

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Section: Development Of the Type 2 Inflammatory Milieu In Eoementioning

confidence: 60%

Novel immunologic mechanisms in eosinophilic esophagitis

Caldwell

Paul

Rothenberg

2017

Current Opinion in Immunology

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“…130 In addition to their altered cytokine signature, the enhanced tissue-trafficking potential of atypical T H 2 cells, coupled with their link to more severe forms of allergic disease, further implicates these cells in disease pathogenesis (Fig 4). 124,129,131 Nonetheless, the origins of these cells and, in particular, the transcription factors driving their fate remain enigmatic.…”

Section: Heterogeneity Of T Cells and Influence Of The Tissue Microenmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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“…The natural killer (NK) cell-associated receptor CD161 (gene symbol KLRB1 ) was previously found to be expressed on a subset of human CCR6 + Th17 cells; to enrich for IL-17A/IFNγ double-producing T cells; and to be increased in inflamed IBD patient biopsies 107 . However, CD161-expressing Treg and Th2 cells have also been reported 108,109 , demonstrating a lack of specificity of CD161 expression for pathogenic Th17 cells. By contrast, expression of the multidrug/xenobiotic transporter, MDR1 ( a.k.a.…”

Section: Cd4+ T Cells In Ibdmentioning

confidence: 99%

Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

Chen

Sundrud

2016

Inflammatory Bowel Diseases

135

104

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Pathogenesis of the inflammatory bowel diseases (IBDs) ulcerative colitis (UC) and Crohn’s disease (CD) involve pro-inflammatory changes within the microbiota, chronic immune-mediated inflammatory responses, and epithelial dysfunction. Converging data from genome-wide association studies (GWAS), mouse models of IBD, and clinical trials indicate that cytokines are key effectors of both normal homeostasis and chronic inflammation in the gut. Yet still many questions remain concerning the role of specific cytokines in different IBDs, within distinct regions of the gut, and with regard cellular mechanisms of action. Here we review current and emerging concepts concerning the role of cytokines in IBD, with a focus on immune regulation, T cell subsets, and potential clinical applications.

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Hematopoietic prostaglandin D synthase defines a proeosinophilic pathogenic effector human TH2 cell subpopulation with enhanced function

Cited by 142 publications

References 52 publications

Novel immunologic mechanisms in eosinophilic esophagitis

Novel immunologic mechanisms in eosinophilic esophagitis

Pathogenic CD4 + T cells in patients with asthma

Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases

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