Anna Carrasco1, Fernando Fernández-Bañares1, Elisabet Pedrosa2, Antonio Salas3, Carme Loras1, Mercè Rosinach1, Montserrat Aceituno2, Xavier Andújar1, Montserrat Forné1, Yamile Zabana1, Maria Esteve4. 1. Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Universitat de Barcelona, Catalonia, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Barcelona, Catalonia, Spain. 2. Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Universitat de Barcelona, Catalonia, Spain. 3. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Barcelona, Catalonia, Spain Department of Pathology, Hospital Universitari Mutua Terrassa, Universitat de Barcelona, Catalonia, Spain. 4. Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Universitat de Barcelona, Catalonia, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Barcelona, Catalonia, Spain mestevecomas@telefonica.net.
Abstract
BACKGROUND AND AIMS: There is very limited information regarding region-specific immunological response in human intestine. We aimed to determine differences in immune compartmentalisation between ileum and colon in healthy and inflamed mucosa. METHODS: T cell profile and its apoptosis were measured by flow cytometry, Th1, Th17, Treg [CD4(+)CD25(+)FOXP3(+)], double positive [DP, CD3(+)CD4(+)CD8(+)] and double negative T cells [DN, CD3(+)CD4(-)CD8(-)], immunohistochemistry [FOXP3, caspase-3], and real-time polymerase chain reaction [PCR] [IFN-γ, IL-17-A, and FOXP3] on biopsies from different regions of healthy intestine and of intestine in inflammatory bowel diseases. RESULTS: Healthy colon showed higher percentages of Treg, Th17, and DN, and lower numbers of DP T cells compared with ileum [p < 0.05]. Some but not all region-specific differences were lost in inflammatory conditions. Disease-specific patterns were found: a Th1/Th17 pattern and a Th17 pattern in Crohn's disease and ulcerative colitis respectively, whereas a reduction in Th1/Th17 was found in microscopic colitis. In colonic Crohn's disease and microscopic colitis, DN T cells had a pattern inverse to that of Th1/Th17 (increase in microscopic colitis [p < 0.05] and decrease in Crohn's disease [p < 0.005]). Higher levels of lymphocyte apoptosis were found in healthy colon compared with the ileal counterparts [p = 0.001]. All forms of colonic inflammation presented a dramatic decrease in apoptosis compared with healthy colon. By contrast ileal Crohn's disease showed higher levels of cleaved-Caspase(+) CD3(+) cells. CONCLUSIONS: Immunological differences exist in healthy gastrointestinal tract. Inflammatory processes overwhelm some location-specific differences, whereas others are maintained. Care has to be taken when analysing immune response in intestinal inflammation, as location-specific differences may be relevant.
BACKGROUND AND AIMS: There is very limited information regarding region-specific immunological response in human intestine. We aimed to determine differences in immune compartmentalisation between ileum and colon in healthy and inflamed mucosa. METHODS: T cell profile and its apoptosis were measured by flow cytometry, Th1, Th17, Treg [CD4(+)CD25(+)FOXP3(+)], double positive [DP, CD3(+)CD4(+)CD8(+)] and double negative T cells [DN, CD3(+)CD4(-)CD8(-)], immunohistochemistry [FOXP3, caspase-3], and real-time polymerase chain reaction [PCR] [IFN-γ, IL-17-A, and FOXP3] on biopsies from different regions of healthy intestine and of intestine in inflammatory bowel diseases. RESULTS: Healthy colon showed higher percentages of Treg, Th17, and DN, and lower numbers of DP T cells compared with ileum [p < 0.05]. Some but not all region-specific differences were lost in inflammatory conditions. Disease-specific patterns were found: a Th1/Th17 pattern and a Th17 pattern in Crohn's disease and ulcerative colitis respectively, whereas a reduction in Th1/Th17 was found in microscopic colitis. In colonic Crohn's disease and microscopic colitis, DN T cells had a pattern inverse to that of Th1/Th17 (increase in microscopic colitis [p < 0.05] and decrease in Crohn's disease [p < 0.005]). Higher levels of lymphocyte apoptosis were found in healthy colon compared with the ileal counterparts [p = 0.001]. All forms of colonic inflammation presented a dramatic decrease in apoptosis compared with healthy colon. By contrast ileal Crohn's disease showed higher levels of cleaved-Caspase(+) CD3(+) cells. CONCLUSIONS: Immunological differences exist in healthy gastrointestinal tract. Inflammatory processes overwhelm some location-specific differences, whereas others are maintained. Care has to be taken when analysing immune response in intestinal inflammation, as location-specific differences may be relevant.
Authors: Liza Konnikova; Tanya O Robinson; Anna H Owings; James F Shirley; Elisabeth Davis; Ying Tang; Sarah Wall; Jian Li; Mohammad H Hasan; Raad Z Gharaibeh; Lybil B Mendoza Alvarez; Lisa K Ryan; Andria Doty; Jack F Chovanec; Michael P O'Connell; Dianne E Grunes; William P Daley; Emeran Mayer; Lin Chang; Julia Liu; Scott B Snapper; Joshua D Milner; Sarah C Glover; Jonathan J Lyons Journal: J Allergy Clin Immunol Date: 2021-04-15 Impact factor: 14.290
Authors: Anna Carrasco; Eva Tristán; Fernando Fernández-Bañares; Albert Martín-Cardona; Montserrat Aceituno; Yamile Zabana; Lourdes Fluvià; José María Hernández; Violeta Lorén; Josep Manyé; Antonio Salas; Xavier Andújar; Carme Loras; Maria Esteve Journal: Immun Inflamm Dis Date: 2022-10