Human colonic myofibroblasts promote expansion of CD4+ CD25 high Foxp3+ regulatory T cells

Iryna Pinchuk, Ellen J. Beswick, Jamal I. Saada, Gushyalatha Boya, David Schmitt, Gottumukkala S. Raju, Julia Brenmoehl, Gerhard Rogler, Victor Reyes, Don W. Powell

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Regulatory T (Treg) cells (CD4 + CD25high FoxP3+) regulate mucosal tolerance; their adoptive transfer prevents or reduces symptoms of colitis in mouse models of inflammatory bowel disease. Colonic CD90+ mesenchymal myofibroblasts and fibroblasts (CMFs) are abundant, nonprofessional antigen-presenting cells in the normal human colonic mucosa that suppress proliferation of activated CD4+ effector T cells. We studied CMF suppressive capacity and evaluated the ability of CMF to induce Treg cells. Methods: Allogeneic cocultures of CD4+ T cells and CMFs, derived from normal mucosa of patients undergoing colectomy for colon cancer or inflamed colonic tissues from patients with ulcerative colitis or Crohn's disease, were used to assess activation of the Treg cells. Results: Coculture of normal CMF with resting or nave CD4+ T cells led to development of cells with a Treg phenotype; it also induced proliferation of a CD25+ CD127- FoxP3+ T cells, which expressed CTLA-4, interleukin-10, and transforming growth factorβ and had suppressive activities. In contrast to dendritic cells, normal CMFs required exogenous interleukin-2 to induce proliferation of naturally occurring Treg cells. Induction of Treg cells by normal CMFs required major histocompatibility complex class II and prostaglandin E 2. CMFs from patients with inflammatory bowel diseases had reduced capacity to induce active Treg cells and increased capacity to transiently generate CD4+CD25+/- CD127+ T cells that express low levels of FoxP3. Conclusions: CMFs suppress the immune response in normal colon tissue and might therefore help maintain colonic mucosal tolerance. Alterations in CMF-mediated induction of Treg cells might promote pathogenesis of inflammatory bowel diseases.

Original languageEnglish (US)
Pages (from-to)2019-2030
Number of pages12
JournalGastroenterology
Volume140
Issue number7
DOIs
StatePublished - Jun 2011

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Myofibroblasts
Regulatory T-Lymphocytes
Fibroblasts
T-Lymphocytes
Inflammatory Bowel Diseases
Coculture Techniques
Mucous Membrane
Adoptive Transfer
Colectomy
Transforming Growth Factors
Antigen-Presenting Cells
Colitis
Prostaglandins E
Major Histocompatibility Complex
Ulcerative Colitis
Crohn Disease
Interleukin-10
Colonic Neoplasms
Dendritic Cells
Interleukin-2

Keywords

  • Immune Regulation
  • Immune Response
  • Inflammation
  • Inflammatory Bowel Disease
  • Stromal Cells

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Pinchuk, I., Beswick, E. J., Saada, J. I., Boya, G., Schmitt, D., Raju, G. S., ... Powell, D. W. (2011). Human colonic myofibroblasts promote expansion of CD4+ CD25 high Foxp3+ regulatory T cells. Gastroenterology, 140(7), 2019-2030. https://doi.org/10.1053/j.gastro.2011.02.059

Human colonic myofibroblasts promote expansion of CD4+ CD25 high Foxp3+ regulatory T cells. / Pinchuk, Iryna; Beswick, Ellen J.; Saada, Jamal I.; Boya, Gushyalatha; Schmitt, David; Raju, Gottumukkala S.; Brenmoehl, Julia; Rogler, Gerhard; Reyes, Victor; Powell, Don W.

In: Gastroenterology, Vol. 140, No. 7, 06.2011, p. 2019-2030.

Research output: Contribution to journalArticle

Pinchuk, I, Beswick, EJ, Saada, JI, Boya, G, Schmitt, D, Raju, GS, Brenmoehl, J, Rogler, G, Reyes, V & Powell, DW 2011, 'Human colonic myofibroblasts promote expansion of CD4+ CD25 high Foxp3+ regulatory T cells', Gastroenterology, vol. 140, no. 7, pp. 2019-2030. https://doi.org/10.1053/j.gastro.2011.02.059
Pinchuk, Iryna ; Beswick, Ellen J. ; Saada, Jamal I. ; Boya, Gushyalatha ; Schmitt, David ; Raju, Gottumukkala S. ; Brenmoehl, Julia ; Rogler, Gerhard ; Reyes, Victor ; Powell, Don W. / Human colonic myofibroblasts promote expansion of CD4+ CD25 high Foxp3+ regulatory T cells. In: Gastroenterology. 2011 ; Vol. 140, No. 7. pp. 2019-2030.
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AU - Boya, Gushyalatha

AU - Schmitt, David

AU - Raju, Gottumukkala S.

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