Regional Specialisation of T Cell Subsets and Apoptosis in the Human Gut Mucosa: Differences Between Ileum and Colon in Healthy Intestine and Inflammatory Bowel Diseases

作者：Carrasco Anna; Fernandez Banares Fernando; Pedrosa Elisabet; Salas Antonio; Loras Carme; Rosinach Merce; Aceituno Montserrat; Andujar Xavier; Forne Montserrat; Zabana Yamile; Esteve Maria^*

来源：Journal of Crohns & Colitis, 2016, 10(9): 1042-1054.

DOI：10.1093/ecco-jcc/jjw066

• Intestinal compartmentalization
• apoptosis
• intestinal lymphocytes

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-gamma, 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.

• 出版日期2016-9