Comprehensive Intestinal T Helper Cell Profiling Reveals Specific Accumulation of IFN-γ+IL-17+Coproducing CD4+ T Cells in Active Inflammatory Bowel Disease

Globig, Anna-Maria; Hennecke, Nadine; Martin, Bianca; Seidl, Maximilian; Ruf, G.; Hasselblatt, Peter; Thimme, Robert; Bengsch, Bertram

doi:10.1097/mib.0000000000000210

Cited by 118 publications

(103 citation statements)

References 39 publications

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“…Interestingly, CD14 + macrophages can induce a T-cell population producing IFNγ and IL-17 in vitro. Consistently, an IFNγ + IL-17 + T-cell population was observed in the intestinal mucosa of CD patients [90]. As for the plasticity in the T-cell development, this double-positive T-cell population is thought to differ from Th17 cells [91].…”

Section: Crohn's Diseasementioning

confidence: 74%

“…Like in CD, IL-23 from CD14 + CD68 + macrophages promote Th17-cell immune responses crucially contributing to the chronic local inflammation of UC [135,136]. Additionally, the T-cell population double positive for IFNγ and IL-17 and originating from Th17 cells is not specific for CD but also present in the intestinal mucosa of patients with active UC [90]. …”

Section: Ulcerative Colitismentioning

confidence: 99%

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The Role of T-Cell Subsets in Chronic Inflammation in Celiac Disease and Inflammatory Bowel Disease Patients: More Common Mechanisms or More Differences?

Hisamatsu

Erben²,

Kühl³

2016

Inflamm Intest Dis

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Background: Chronic intestinal inflammation due to noninfectious causes represents a growing health issue all over the world. Celiac disease as well as inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative and microscopic colitis involve uncontrolled T-cell activation and T-cell-mediated damage as common denominators. Therefore, diagnosis and treatment decisions clearly benefit from the knowledge of the intricacies of the systemic and the local T-cell activity. Summary: Depending on the cytokine milieu, CD4⁺ T cells can differentiate into proinflammatory T helper 1 (Th1), anti-inflammatory Th2, antimicrobial Th17, pleiotropic Th9, tissue-instructing Th22 cells, and in the regulatory compartment forkhead box protein 3⁺ Treg, suppressive Tr1 or Th3 cells. Additionally, follicular Th cells provide B-cell help in antibody class switching; cytotoxic CD8⁺ T cells target virus-infected or tumor cells. This review discusses our current knowledge on the contribution of defined T-cell subpopulations to establishing and maintaining chronic intestinal inflammation in either of the above entities. It also puts emphasis on the differences in the prevalence of these diseases between Eastern and Western countries. Key Messages: In celiac disease, the driving role of T cells in the lamina propria and in the epithelium mainly specific for two defined antigens is well established. Differences in genetics and lifestyle between Western and Eastern countries were instrumental in understanding underlying mechanisms. In IBD, the vast amount of potential antigens and the corresponding antigen-specific T cells makes it unlikely to find universal triggers. Increased mucosal CD4⁺ regulatory T cells in all four entities fail to control or abrogate local inflammatory processes. Thus, prevailing differences in the functional T-cell subtypes driving chronic intestinal inflammation in celiac disease and IBD at best allow some overlap in the treatment options for either disease.

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Section: Crohn's Diseasementioning

confidence: 74%

Section: Ulcerative Colitismentioning

confidence: 99%

The Role of T-Cell Subsets in Chronic Inflammation in Celiac Disease and Inflammatory Bowel Disease Patients: More Common Mechanisms or More Differences?

Hisamatsu

Erben²,

Kühl³

2016

Inflamm Intest Dis

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“…T cells. This dual Th1 and Th17 phenotype drives autoimmune pathology, suggesting a key role for infiltrating DC in the pathogenesis of these diseases [64,152,153]. DC derived from human inflammatory tissues express CD1a, CD1c, FceR1, CD206, CD14, CD11b, M-CSFR and ZBTB46 [64].…”

Section: Inflammatory DCmentioning

confidence: 99%

Human dendritic cell subsets and function in health and disease

O’Keeffe

Mok

Radford

2015

Cell. Mol. Life Sci.

165

149

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The method of choice for the development of new vaccines is to target distinct dendritic cell subsets with antigen in vivo and to harness their function in situ to enhance cell-mediated immunity or induce tolerance to specific antigens. The innate functions of dendritic cells themselves may also be targeted by inhibitors or activators that would target a specific function such as interferon production, potentially important in autoimmune disease and chronic viral infections. Importantly targeting dendritic cells requires detailed knowledge of both the surface phenotype and function of each dendritic cell subset, including how they may respond to different types of vaccine adjuvants, their ability to produce soluble mediators and to process and present antigens and induce priming of naïve T cells. This review summarizes our knowledge of the functional attributes of the human dendritic cell subsets in the steady state and upon activation and their roles in human disease.

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“…Th17.1 cells which express chemokine receptors; CXCR3, CCR6: C-type lectin; CD161: and IL-23R (Annunziato et al, 2007, Nistala andWedderburn, 2009), and have been identified in arthritic patients (Cosmi et al, 2008, Maggi et al, 2014, Nistala and Wedderburn, 2009), CD patients (Annunziato et al, 2007, Ramesh et al, 2014, IBD patients (Globig et al, 2014), and AS patients (Limon-Camacho et al, 2012, Zhang et al, 2012. Th17.1 phenotype can be distinguished from classical, memory Th1 cells based on the expression of CD161, where it is not expressed on Th1 cells (Annunziato et al, 2013, Cosmi et al, 2008.…”

Section: 6) Memory Th171 Cells -Phenotypementioning

confidence: 99%

The role of human CD1c+ DCs at activating innate and adaptive immune responses

Mok¹

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In humans, several dendritic cell (DC) subsets have been identified, including the CD1c + DCs, CD141 + DCs and plasmacytoid DC (pDC). It has been suggested that human CD141 + DCs play a role in cross-presentation leading to the induction of cytotoxic T lymphocyte (CTL) responses that are important for immunity against tumours and intracellular pathogens. pDCs are known to be major responders against viruses through secretion of Type I interferons (IFNs).

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Comprehensive Intestinal T Helper Cell Profiling Reveals Specific Accumulation of IFN-γ+IL-17+Coproducing CD4+ T Cells in Active Inflammatory Bowel Disease

Cited by 118 publications

References 39 publications

The Role of T-Cell Subsets in Chronic Inflammation in Celiac Disease and Inflammatory Bowel Disease Patients: More Common Mechanisms or More Differences?

The Role of T-Cell Subsets in Chronic Inflammation in Celiac Disease and Inflammatory Bowel Disease Patients: More Common Mechanisms or More Differences?

Human dendritic cell subsets and function in health and disease

The role of human CD1c+ DCs at activating innate and adaptive immune responses

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