Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients
The drug targets IL23 and IL12 regulate pathogenicity and plasticity of intestinal Th17 cells in Crohn's disease (CD) and ulcerative colitis (UC), the two most common inflammatory bowel diseases (IBD). However, studies examining Th17 dysregulation in mesenteric lymph nodes (mLNs) of these patie...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01177/full |
| _version_ | 1818285129845440512 |
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| author | Marwa Bsat Laurence Chapuy Manuel Rubio Ramses Wassef Carole Richard Frank Schwenter Rasmy Loungnarath Geneviève Soucy Heena Mehta Marika Sarfati |
| author_facet | Marwa Bsat Laurence Chapuy Manuel Rubio Ramses Wassef Carole Richard Frank Schwenter Rasmy Loungnarath Geneviève Soucy Heena Mehta Marika Sarfati |
| author_sort | Marwa Bsat |
| collection | DOAJ |
| description | The drug targets IL23 and IL12 regulate pathogenicity and plasticity of intestinal Th17 cells in Crohn's disease (CD) and ulcerative colitis (UC), the two most common inflammatory bowel diseases (IBD). However, studies examining Th17 dysregulation in mesenteric lymph nodes (mLNs) of these patients are rare. We showed that in mLNs, CD could be distinguished from UC by increased frequencies of CCR6+CXCR3−RORγ+Tbet−CD4+ (Th17) memory T cells enriched in CD62Llow effector memory T cells (TEM), and their differentially expressed molecular profile. Th17 TEM cells (expressing IL17A, IL17F, RORC, and STAT3) displayed a higher pathogenic/cytotoxic (IL23R, IL18RAP, and GZMB, CD160, PRF1) gene signature in CD relative to UC, while non-pathogenic/regulatory genes (IL9, FOXP3, CTLA4) were more elevated in UC. In both CD and UC, IL12 but not IL23, augmented IFNγ expression in Th17 TEM and switched their molecular profile toward an ex-Th17 (Th1*)-biased transcriptomic signature (increased IFNG, and decreased TCF7, IL17A), suggesting that Th17 plasticity occurs in mLNs before their recruitment to inflamed colon. We propose that differences observed between Th17 cell frequencies and their molecular profile in CD and UC might have implications in understanding disease pathogenesis, and thus, therapeutic management of patients with IBD. |
| first_indexed | 2024-12-13T01:03:48Z |
| format | Article |
| id | doaj.art-a15e208700814ddc8ddeef757aeb29d3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T01:03:48Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a15e208700814ddc8ddeef757aeb29d32022-12-22T00:04:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.01177460653Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis PatientsMarwa Bsat0Laurence Chapuy1Manuel Rubio2Ramses Wassef3Carole Richard4Frank Schwenter5Rasmy Loungnarath6Geneviève Soucy7Heena Mehta8Marika Sarfati9Immunoregulation Laboratory, Centre de Recherche du CHUM (CRCHUM), Montreal, QC, CanadaImmunoregulation Laboratory, Centre de Recherche du CHUM (CRCHUM), Montreal, QC, CanadaImmunoregulation Laboratory, Centre de Recherche du CHUM (CRCHUM), Montreal, QC, CanadaDepartment of Gastrointestinal Surgery, CHUM, Montreal, QC, CanadaDepartment of Gastrointestinal Surgery, CHUM, Montreal, QC, CanadaDepartment of Gastrointestinal Surgery, CHUM, Montreal, QC, CanadaDepartment of Gastrointestinal Surgery, CHUM, Montreal, QC, CanadaDepartment of Pathology, CHUM, Montreal, QC, CanadaImmunoregulation Laboratory, Centre de Recherche du CHUM (CRCHUM), Montreal, QC, CanadaImmunoregulation Laboratory, Centre de Recherche du CHUM (CRCHUM), Montreal, QC, CanadaThe drug targets IL23 and IL12 regulate pathogenicity and plasticity of intestinal Th17 cells in Crohn's disease (CD) and ulcerative colitis (UC), the two most common inflammatory bowel diseases (IBD). However, studies examining Th17 dysregulation in mesenteric lymph nodes (mLNs) of these patients are rare. We showed that in mLNs, CD could be distinguished from UC by increased frequencies of CCR6+CXCR3−RORγ+Tbet−CD4+ (Th17) memory T cells enriched in CD62Llow effector memory T cells (TEM), and their differentially expressed molecular profile. Th17 TEM cells (expressing IL17A, IL17F, RORC, and STAT3) displayed a higher pathogenic/cytotoxic (IL23R, IL18RAP, and GZMB, CD160, PRF1) gene signature in CD relative to UC, while non-pathogenic/regulatory genes (IL9, FOXP3, CTLA4) were more elevated in UC. In both CD and UC, IL12 but not IL23, augmented IFNγ expression in Th17 TEM and switched their molecular profile toward an ex-Th17 (Th1*)-biased transcriptomic signature (increased IFNG, and decreased TCF7, IL17A), suggesting that Th17 plasticity occurs in mLNs before their recruitment to inflamed colon. We propose that differences observed between Th17 cell frequencies and their molecular profile in CD and UC might have implications in understanding disease pathogenesis, and thus, therapeutic management of patients with IBD.https://www.frontiersin.org/article/10.3389/fimmu.2019.01177/fullTh17 cellsmesenteric lymph nodesinflammatory bowel diseasehumanplasticity |
| spellingShingle | Marwa Bsat Laurence Chapuy Manuel Rubio Ramses Wassef Carole Richard Frank Schwenter Rasmy Loungnarath Geneviève Soucy Heena Mehta Marika Sarfati Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients Frontiers in Immunology Th17 cells mesenteric lymph nodes inflammatory bowel disease human plasticity |
| title | Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients |
| title_full | Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients |
| title_fullStr | Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients |
| title_full_unstemmed | Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients |
| title_short | Differential Pathogenic Th17 Profile in Mesenteric Lymph Nodes of Crohn's Disease and Ulcerative Colitis Patients |
| title_sort | differential pathogenic th17 profile in mesenteric lymph nodes of crohn s disease and ulcerative colitis patients |
| topic | Th17 cells mesenteric lymph nodes inflammatory bowel disease human plasticity |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01177/full |
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