TY - JOUR
T1 - IL-22+ CD4+ T cells are associated with therapeutic Trichuris trichiura infection in an ulcerative colitis patient
AU - Broadhurst, Mara J.
AU - Leung, Jacqueline M.
AU - Kashyap, Vikram
AU - McCune, Joseph M.
AU - Mahadevan, Uma
AU - McKerrow, James H.
AU - Loke, P'ng
PY - 2010/12/1
Y1 - 2010/12/1
N2 - Ulcerative colitis, a type of inflammatory bowel disease, is less common in countries endemic for helminth infections, suggesting that helminth colonization may have the potential to regulate intestinal inflammation in inflammatory bowel diseases. Indeed, therapeutic effects of experimental helminth infection have been reported in both animal models and clinical trials. Here, we provide a comprehensive cellular and molecular portrait of dynamic changes in the intestinal mucosa of an individual who infected himself with Trichuris trichiura to treat his symptoms of ulcerative colitis. Tissue with active colitis had a prominent population of mucosal T helper (TH) cells that produced the inflammatory cytokine interleukin-17 (IL-17) but not IL-22, a cytokine involved in mucosal healing. After helminth exposure, the disease went into remission, and IL-22-producing TH cells accumulated in the mucosa. Genes involved in carbohydrate and lipid metabolism were up-regulated in helminth-colonized tissue, whereas tissues with active colitis showed up-regulation of proinflammatory genes such as IL-17, IL-13RA2, and CHI3L1. Therefore, T. trichiura colonization of the intestine may reduce symptomatic colitis by promoting goblet cell hyperplasia and mucus production through TH2 cytokines and IL-22. Improved understanding of the physiological effects of helminth infection may lead to new therapies for inflammatory bowel diseases.
AB - Ulcerative colitis, a type of inflammatory bowel disease, is less common in countries endemic for helminth infections, suggesting that helminth colonization may have the potential to regulate intestinal inflammation in inflammatory bowel diseases. Indeed, therapeutic effects of experimental helminth infection have been reported in both animal models and clinical trials. Here, we provide a comprehensive cellular and molecular portrait of dynamic changes in the intestinal mucosa of an individual who infected himself with Trichuris trichiura to treat his symptoms of ulcerative colitis. Tissue with active colitis had a prominent population of mucosal T helper (TH) cells that produced the inflammatory cytokine interleukin-17 (IL-17) but not IL-22, a cytokine involved in mucosal healing. After helminth exposure, the disease went into remission, and IL-22-producing TH cells accumulated in the mucosa. Genes involved in carbohydrate and lipid metabolism were up-regulated in helminth-colonized tissue, whereas tissues with active colitis showed up-regulation of proinflammatory genes such as IL-17, IL-13RA2, and CHI3L1. Therefore, T. trichiura colonization of the intestine may reduce symptomatic colitis by promoting goblet cell hyperplasia and mucus production through TH2 cytokines and IL-22. Improved understanding of the physiological effects of helminth infection may lead to new therapies for inflammatory bowel diseases.
UR - http://www.scopus.com/inward/record.url?scp=78649823511&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649823511&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.3001500
DO - 10.1126/scitranslmed.3001500
M3 - Article
C2 - 21123809
AN - SCOPUS:78649823511
SN - 1946-6234
VL - 2
JO - Science translational medicine
JF - Science translational medicine
IS - 60
M1 - 60ra88
ER -