Treatment of experimental colitis by oral tolerance induction

A central role for suppressor lymphocytes

Yaron Ilan, Sarah Weksler-Zangen, Shomron Ben-Horin, Judith Diment, Bernhard Sauter, Elazar Rabbani, Dean Engelhardt, Namita Roy Chowdhury, Jayanta Roy-Chowdhury, Eran Goldin

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: Inflammatory bowel diseases (IBD) are immune-mediated disorders wherein an imbalance between proinflammatory (Th1) and antiinflammatory (Th2) cytokines is thought to play a role in the pathogenesis. The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Rats received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Splenocytes harvested from tolerized and control rats were transplanted into irradiated naive rats. RESULTS: Feeding of colitis- extracted proteins ameliorated colonic inflammation, as shown by reduction of colonic ulcerations, as well as decreased diarrhea, intestine and peritoneal adhesions, wall thickness, and edema. A marked reduction of the fraction of injured colonic area and colon weight, and decrease in colon weight, were observed in tolerized rats versus controls. Histological parameters for colitis were markedly improved in tolerized animals that showed significant reduction in inflammatory response and mucosal ulcerations. Tolerized rats developed an increase in TGFβ1 and a decrease in IFNγ serum levels. TNBS- induced colitis was significantly attenuated in naive recipients of splenocytes from tolerized rats, compared with rats that received splenocytes from control donors. CONCLUSIONS: Induction of oral tolerance to colitis- extracted proteins downregulates the anticolon immune response, thereby ameliorating experimental colitis. Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response. (C) 2000 by Am. Coll. of Gastroenterology.

Original languageEnglish (US)
Pages (from-to)966-973
Number of pages8
JournalAmerican Journal of Gastroenterology
Volume95
Issue number4
DOIs
StatePublished - Apr 2000

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Colitis
Lymphocytes
Trinitrobenzenesulfonic Acid
Colon
Therapeutics
Proteins
Anti-Inflammatory Agents
Weights and Measures
Immune Tolerance
Immune System Diseases
Gastroenterology
Inflammatory Bowel Diseases
Intestines
Diarrhea
Edema
Down-Regulation
Cytokines
Inflammation
Serum

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ilan, Y., Weksler-Zangen, S., Ben-Horin, S., Diment, J., Sauter, B., Rabbani, E., ... Goldin, E. (2000). Treatment of experimental colitis by oral tolerance induction: A central role for suppressor lymphocytes. American Journal of Gastroenterology, 95(4), 966-973. https://doi.org/10.1016/S0002-9270(00)00727-9

Treatment of experimental colitis by oral tolerance induction : A central role for suppressor lymphocytes. / Ilan, Yaron; Weksler-Zangen, Sarah; Ben-Horin, Shomron; Diment, Judith; Sauter, Bernhard; Rabbani, Elazar; Engelhardt, Dean; Roy Chowdhury, Namita; Roy-Chowdhury, Jayanta; Goldin, Eran.

In: American Journal of Gastroenterology, Vol. 95, No. 4, 04.2000, p. 966-973.

Research output: Contribution to journalArticle

Ilan, Y, Weksler-Zangen, S, Ben-Horin, S, Diment, J, Sauter, B, Rabbani, E, Engelhardt, D, Roy Chowdhury, N, Roy-Chowdhury, J & Goldin, E 2000, 'Treatment of experimental colitis by oral tolerance induction: A central role for suppressor lymphocytes', American Journal of Gastroenterology, vol. 95, no. 4, pp. 966-973. https://doi.org/10.1016/S0002-9270(00)00727-9
Ilan, Yaron ; Weksler-Zangen, Sarah ; Ben-Horin, Shomron ; Diment, Judith ; Sauter, Bernhard ; Rabbani, Elazar ; Engelhardt, Dean ; Roy Chowdhury, Namita ; Roy-Chowdhury, Jayanta ; Goldin, Eran. / Treatment of experimental colitis by oral tolerance induction : A central role for suppressor lymphocytes. In: American Journal of Gastroenterology. 2000 ; Vol. 95, No. 4. pp. 966-973.
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abstract = "OBJECTIVE: Inflammatory bowel diseases (IBD) are immune-mediated disorders wherein an imbalance between proinflammatory (Th1) and antiinflammatory (Th2) cytokines is thought to play a role in the pathogenesis. The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Rats received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Splenocytes harvested from tolerized and control rats were transplanted into irradiated naive rats. RESULTS: Feeding of colitis- extracted proteins ameliorated colonic inflammation, as shown by reduction of colonic ulcerations, as well as decreased diarrhea, intestine and peritoneal adhesions, wall thickness, and edema. A marked reduction of the fraction of injured colonic area and colon weight, and decrease in colon weight, were observed in tolerized rats versus controls. Histological parameters for colitis were markedly improved in tolerized animals that showed significant reduction in inflammatory response and mucosal ulcerations. Tolerized rats developed an increase in TGFβ1 and a decrease in IFNγ serum levels. TNBS- induced colitis was significantly attenuated in naive recipients of splenocytes from tolerized rats, compared with rats that received splenocytes from control donors. CONCLUSIONS: Induction of oral tolerance to colitis- extracted proteins downregulates the anticolon immune response, thereby ameliorating experimental colitis. Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response. (C) 2000 by Am. Coll. of Gastroenterology.",
author = "Yaron Ilan and Sarah Weksler-Zangen and Shomron Ben-Horin and Judith Diment and Bernhard Sauter and Elazar Rabbani and Dean Engelhardt and {Roy Chowdhury}, Namita and Jayanta Roy-Chowdhury and Eran Goldin",
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AU - Weksler-Zangen, Sarah

AU - Ben-Horin, Shomron

AU - Diment, Judith

AU - Sauter, Bernhard

AU - Rabbani, Elazar

AU - Engelhardt, Dean

AU - Roy Chowdhury, Namita

AU - Roy-Chowdhury, Jayanta

AU - Goldin, Eran

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N2 - OBJECTIVE: Inflammatory bowel diseases (IBD) are immune-mediated disorders wherein an imbalance between proinflammatory (Th1) and antiinflammatory (Th2) cytokines is thought to play a role in the pathogenesis. The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Rats received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Splenocytes harvested from tolerized and control rats were transplanted into irradiated naive rats. RESULTS: Feeding of colitis- extracted proteins ameliorated colonic inflammation, as shown by reduction of colonic ulcerations, as well as decreased diarrhea, intestine and peritoneal adhesions, wall thickness, and edema. A marked reduction of the fraction of injured colonic area and colon weight, and decrease in colon weight, were observed in tolerized rats versus controls. Histological parameters for colitis were markedly improved in tolerized animals that showed significant reduction in inflammatory response and mucosal ulcerations. Tolerized rats developed an increase in TGFβ1 and a decrease in IFNγ serum levels. TNBS- induced colitis was significantly attenuated in naive recipients of splenocytes from tolerized rats, compared with rats that received splenocytes from control donors. CONCLUSIONS: Induction of oral tolerance to colitis- extracted proteins downregulates the anticolon immune response, thereby ameliorating experimental colitis. Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response. (C) 2000 by Am. Coll. of Gastroenterology.

AB - OBJECTIVE: Inflammatory bowel diseases (IBD) are immune-mediated disorders wherein an imbalance between proinflammatory (Th1) and antiinflammatory (Th2) cytokines is thought to play a role in the pathogenesis. The aim of this study was to test whether induction of oral tolerance to proteins extracted from inflammatory colon alleviates experimental colitis, and whether oral tolerization mediated by suppressor cells can induce immune tolerance. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Rats received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Splenocytes harvested from tolerized and control rats were transplanted into irradiated naive rats. RESULTS: Feeding of colitis- extracted proteins ameliorated colonic inflammation, as shown by reduction of colonic ulcerations, as well as decreased diarrhea, intestine and peritoneal adhesions, wall thickness, and edema. A marked reduction of the fraction of injured colonic area and colon weight, and decrease in colon weight, were observed in tolerized rats versus controls. Histological parameters for colitis were markedly improved in tolerized animals that showed significant reduction in inflammatory response and mucosal ulcerations. Tolerized rats developed an increase in TGFβ1 and a decrease in IFNγ serum levels. TNBS- induced colitis was significantly attenuated in naive recipients of splenocytes from tolerized rats, compared with rats that received splenocytes from control donors. CONCLUSIONS: Induction of oral tolerance to colitis- extracted proteins downregulates the anticolon immune response, thereby ameliorating experimental colitis. Suppressor lymphocytes mediate the tolerance by induction of a shift from a proinflammatory to an antiinflammatory immune response. (C) 2000 by Am. Coll. of Gastroenterology.

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