Pediatric Crohn disease is characterized by Th1 in the terminal ileum and Th1/Th17 immune response in the colon

Mlakar, Ana Savić; Hojsak, Iva; Jergović, Mladen; Čimić, Samir; Bendelja, Krešo

doi:10.1007/s00431-017-3076-8

Cited by 15 publications

(10 citation statements)

References 21 publications

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“…Previously, we have shown that N-CMFs suppress IFN-γ production by activated T cells in a PD-L1-dependent manner ( 32 ). An increase in the IFN-γ-producing Th1 cells in CD LP and a decrease in UC LP have been recently observed by several investigators ( 43 – 45 ). We also observed an increase in IFN-γ levels in the inflamed mucosa of patients with CD colitis (Figure 5 ).…”

Section: Resultsmentioning

confidence: 62%

Expression of Programmed Death-Ligand 1 by Human Colonic CD90+ Stromal Cells Differs Between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells

Beswick¹,

Grim

Singh

et al. 2018

Front. Immunol.

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Background and AimsThe role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90+ colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses.MethodsTissues and cells derived from Crohn’s disease (CD), ulcerative colitis (UC), and healthy individuals (N) were studied in situ, ex vivo, and in culture.ResultsA significant increase in programmed death-ligand 1 (PD-L1) was observed in the inflamed UC colonic mucosa when compared to the non-inflamed matched tissue samples, CD, and healthy controls. UC-CMFs were among the major populations in the colonic mucosa contributing to the enhanced PD-L1 expression. In contrast, PD-L1 expression was decreased in CD-CMFs. When compared to CD-CMFs and N-CMFs, UC-CMFs demonstrated stronger suppression of IL-2, Th1 transcriptional factor Tbet, and IFN-γ expression by CD3/CD28-activated CD4+ T cells, and this process was PD-L1 dependent. Similar observations were made when differentiated Th1 cells were cocultured with UC-CMFs. In contrast, CD-CMFs showed reduced capacity to suppress Th1 cell activity and addition of recombinant PD-L1 Fc to CD-CMF:T cell cocultures partially restored the suppression of the Th1 type responses.ConclusionWe present evidence showing that increased PD-L1 expression suppresses Th1 cell activity in UC. In contrast, loss of PD-L1 expression observed in CD contributes to the persistence of the Th1 inflammatory milieu in CD. Our data suggest that dysregulation of the Th1 responses in the inflamed colonic mucosa of IBD patients is promoted by the alterations in PD-L1 expression in the mucosal mesenchymal stromal cell compartment.

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Section: Resultsmentioning

confidence: 62%

Expression of Programmed Death-Ligand 1 by Human Colonic CD90+ Stromal Cells Differs Between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells

Beswick¹,

Grim

Singh

et al. 2018

Front. Immunol.

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“…Indeed, Th2 related cytokines such as IL-4, IL-5, IL-6, and IL-13 are increased in UC patients [197,198]. On the contrary, Th1-related cytokines such as TNF, IFN-γ, and IL-12 are increased in the colonic mucosa of CD [199,200].…”

Section: Inflammatory Bowel Diseasesmentioning

confidence: 99%

Therapeutic Functions of Stem Cells from Oral Cavity: An Update

Yang

Shin

Seo

et al. 2020

IJMS

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Adult stem cells have been developed as therapeutics for tissue regeneration and immune regulation due to their self-renewing, differentiating, and paracrine functions. Recently, a variety of adult stem cells from the oral cavity have been discovered, and these dental stem cells mostly exhibit the characteristics of mesenchymal stem cells (MSCs). Dental MSCs can be applied for the replacement of dental and oral tissues against various tissue-damaging conditions including dental caries, periodontitis, and oral cancers, as well as for systemic regulation of excessive inflammation in immune disorders, such as autoimmune diseases and hypersensitivity. Therefore, in this review, we summarized and updated the types of dental stem cells and their functions to exert therapeutic efficacy against diseases.

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“…In addition, it has been demonstrated that IL-5, IL-13, IL-15 and IL-33 mRNA levels in DC patients were significantly increased when compared to both DC and control [5]. Interestingly, it was shown that pediatric CD is characterized by Th1 in the terminal ileum and Th1/Th17 immune response in the colon [54]. However, currently it is considered that Th1 and Th2 immune responses do not represent the complexity of immune responses measured by intestinal T cells.…”

Section: Revisiting Th1 and Th2 Lymphocytesmentioning

confidence: 99%

Mucosal Immunology in the Inflammatory Bowel Diseases

Degasperi¹

2020

Biological Therapy for Inflammatory Bowel Disease

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Inflammatory bowel disease (IBD) includes two major phenotypes, Crohn's disease and ulcerative colitis, which have different clinical characteristics and immune response profiles. Dysregulation of the intestinal immune response with elevated secretion of proinflammatory cytokines is a hallmark of IBD. In this chapter, we will characterize the cells of the innate and adaptive immunity involved in the pathogenesis of IBD. Innate lymphoid cells as well as dendritic cells, neutrophils, macrophages, B cells and T cells, including Th1 and Th2, Th9 and Th17 cells will be specifically characterized in this scenario. The cross talks and cytokine-mediated regulation of these cells with emphasis on cytokines IL-17, IL-22 and IL-23 will also be emphasized.

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Pediatric Crohn disease is characterized by Th1 in the terminal ileum and Th1/Th17 immune response in the colon

Cited by 15 publications

References 21 publications

Expression of Programmed Death-Ligand 1 by Human Colonic CD90+ Stromal Cells Differs Between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells

Expression of Programmed Death-Ligand 1 by Human Colonic CD90+ Stromal Cells Differs Between Ulcerative Colitis and Crohn’s Disease and Determines Their Capacity to Suppress Th1 Cells

Therapeutic Functions of Stem Cells from Oral Cavity: An Update

Mucosal Immunology in the Inflammatory Bowel Diseases

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