Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease.
In the recent years, the incidence of inflammatory bowel disease (IBD) has dramatically increased in young subjects, however, the pathogenesis of paediatric IBD is poorly investigated. In this study we aimed to evaluate the cytokine pattern and the phenotype of cytokine producing cells in the intest...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182313&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850076234902405120 |
|---|---|
| author | Serena Vitale Caterina Strisciuglio Laura Pisapia Erasmo Miele Pasquale Barba Alessandra Vitale Sabrina Cenni Virginia Bassi Mariantonia Maglio Giovanna Del Pozzo Riccardo Troncone Annamaria Staiano Carmen Gianfrani |
| author_facet | Serena Vitale Caterina Strisciuglio Laura Pisapia Erasmo Miele Pasquale Barba Alessandra Vitale Sabrina Cenni Virginia Bassi Mariantonia Maglio Giovanna Del Pozzo Riccardo Troncone Annamaria Staiano Carmen Gianfrani |
| author_sort | Serena Vitale |
| collection | DOAJ |
| description | In the recent years, the incidence of inflammatory bowel disease (IBD) has dramatically increased in young subjects, however, the pathogenesis of paediatric IBD is poorly investigated. In this study we aimed to evaluate the cytokine pattern and the phenotype of cytokine producing cells in the intestinal mucosa of paediatric patients affected by Crohn's disease (CD) or ulcerative colitis (UC) and of non-IBD healthy controls (HC). Cytokine (IL-15, TNF-α, INF-γ) production was analyzed at basal condition and after mitogen stimulation either intracellularly by flow cytometry or in intestinal cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). A higher frequency of enterocytes (EpCam+ cells) was observed in UC patients compared to CD or HC. An expansion of enterocytes producing IL-15 and TNF-α were found in IBD patients compared to HC. A marked expression of IL-15 in the intestinal epithelium of IBD patients was further confirmed by immunohistochemistry. Myeloid dendritic (CD11c+) cells producing TNF-α and INF-γ were increased in IBD biopsies. Unexpectedly, only after a strong mitogen stimulus, as phytohaemagglutinin, the frequency of CD3+ cells producing IFN-γ was increased in IBD compared to control intestinal mucosa. Interestingly, functional studies performed on organ cultures of intestinal biopsies with neutralizing anti-IL-15 monoclonal antibody showed a marked reduction of mononuclear cell activation, proliferation of crypt enterocytes, as well as a reduction of TNF-α release in organ culture supernatants. In conclusion, we found that in the gut mucosa of IBD children both enterocytes and dendritic cells produce proinflammatory cytokines. The over-expression of IL-15 by enterocytes in IBD intestine and the reduced IBD inflammation by IL-15 blockage suggests that this cytokine could be a therapeutic target in IBD. |
| format | Article |
| id | doaj-art-d9e8db8702f94fdfa323e216b18606d5 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d9e8db8702f94fdfa323e216b18606d52025-08-20T02:46:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018231310.1371/journal.pone.0182313Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease.Serena VitaleCaterina StrisciuglioLaura PisapiaErasmo MielePasquale BarbaAlessandra VitaleSabrina CenniVirginia BassiMariantonia MaglioGiovanna Del PozzoRiccardo TronconeAnnamaria StaianoCarmen GianfraniIn the recent years, the incidence of inflammatory bowel disease (IBD) has dramatically increased in young subjects, however, the pathogenesis of paediatric IBD is poorly investigated. In this study we aimed to evaluate the cytokine pattern and the phenotype of cytokine producing cells in the intestinal mucosa of paediatric patients affected by Crohn's disease (CD) or ulcerative colitis (UC) and of non-IBD healthy controls (HC). Cytokine (IL-15, TNF-α, INF-γ) production was analyzed at basal condition and after mitogen stimulation either intracellularly by flow cytometry or in intestinal cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). A higher frequency of enterocytes (EpCam+ cells) was observed in UC patients compared to CD or HC. An expansion of enterocytes producing IL-15 and TNF-α were found in IBD patients compared to HC. A marked expression of IL-15 in the intestinal epithelium of IBD patients was further confirmed by immunohistochemistry. Myeloid dendritic (CD11c+) cells producing TNF-α and INF-γ were increased in IBD biopsies. Unexpectedly, only after a strong mitogen stimulus, as phytohaemagglutinin, the frequency of CD3+ cells producing IFN-γ was increased in IBD compared to control intestinal mucosa. Interestingly, functional studies performed on organ cultures of intestinal biopsies with neutralizing anti-IL-15 monoclonal antibody showed a marked reduction of mononuclear cell activation, proliferation of crypt enterocytes, as well as a reduction of TNF-α release in organ culture supernatants. In conclusion, we found that in the gut mucosa of IBD children both enterocytes and dendritic cells produce proinflammatory cytokines. The over-expression of IL-15 by enterocytes in IBD intestine and the reduced IBD inflammation by IL-15 blockage suggests that this cytokine could be a therapeutic target in IBD.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182313&type=printable |
| spellingShingle | Serena Vitale Caterina Strisciuglio Laura Pisapia Erasmo Miele Pasquale Barba Alessandra Vitale Sabrina Cenni Virginia Bassi Mariantonia Maglio Giovanna Del Pozzo Riccardo Troncone Annamaria Staiano Carmen Gianfrani Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease. PLoS ONE |
| title | Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease. |
| title_full | Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease. |
| title_fullStr | Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease. |
| title_full_unstemmed | Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease. |
| title_short | Cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease. |
| title_sort | cytokine production profile in intestinal mucosa of paediatric inflammatory bowel disease |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182313&type=printable |
| work_keys_str_mv | AT serenavitale cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT caterinastrisciuglio cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT laurapisapia cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT erasmomiele cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT pasqualebarba cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT alessandravitale cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT sabrinacenni cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT virginiabassi cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT mariantoniamaglio cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT giovannadelpozzo cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT riccardotroncone cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT annamariastaiano cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease AT carmengianfrani cytokineproductionprofileinintestinalmucosaofpaediatricinflammatoryboweldisease |