Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa

Jamal I. Saada, Iryna Pinchuk, Carlos A. Barrera, Patrick A. Adegboyega, Giovanni Suarez, Randy C. Mifflin, John F. Di Mari, Victor Reyes, Don W. Powell

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The human gastrointestinal mucosa is exposed to a diverse normal microflora and dietary Ags and is a common site of entry for pathogens. The mucosal immune system must respond to these diverse signals with either the initiation of immunity or tolerance. APCs are important accessory cells that modulate T cell responses which initiate and maintain adaptive immunity. The ability of APCs to communicate with CD4+ T cells is largely dependent on the expression of class II MHC molecules by the APCs. Using immunohistochemistry, confocal microscopy, and low cytometry, we demonstrate that α-smooth muscle actin+, CB90+ subepithelial myofibroblasts (stromal cells) constitutively express class II MHC molecules in normal colonic mucosa and that they are distinct from professional APCs such as macrophages and dendritic cells. Primary isolates of human colonic myofibroblasts (CMFs) cultured in vitro were able to stimulate allogeneic CD4+ T cell proliferation. This process was dependent on class II MHC and CD80/B6 costimulatory molecule expression by the myofibroblasts. We also demonstrate that CMFs, engineered to express a specific DR4 allele, can process and present human serum albumin to a human serum albumin-specific and DR4 allele-restricted T cell hybridoma. These studies characterize a novel cell phenotype which, due to its strategic location and class II MHC expression, may be involved in capture of Ags that cross the epithelial barrier and present them to lamina propria CD4+ T cells. Thus, human CMFs may be important in regulating local immunity in the colon.

Original languageEnglish (US)
Pages (from-to)5968-5979
Number of pages12
JournalJournal of Immunology
Volume177
Issue number9
StatePublished - Nov 1 2006

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Myofibroblasts
Mucous Membrane
T-Lymphocytes
Serum Albumin
Immunity
Alleles
Hybridomas
Adaptive Immunity
Stromal Cells
Confocal Microscopy
Dendritic Cells
Smooth Muscle
Actins
Immune System
Colon
Immunohistochemistry
Macrophages
Cell Proliferation
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Saada, J. I., Pinchuk, I., Barrera, C. A., Adegboyega, P. A., Suarez, G., Mifflin, R. C., ... Powell, D. W. (2006). Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa. Journal of Immunology, 177(9), 5968-5979.

Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa. / Saada, Jamal I.; Pinchuk, Iryna; Barrera, Carlos A.; Adegboyega, Patrick A.; Suarez, Giovanni; Mifflin, Randy C.; Di Mari, John F.; Reyes, Victor; Powell, Don W.

In: Journal of Immunology, Vol. 177, No. 9, 01.11.2006, p. 5968-5979.

Research output: Contribution to journalArticle

Saada, JI, Pinchuk, I, Barrera, CA, Adegboyega, PA, Suarez, G, Mifflin, RC, Di Mari, JF, Reyes, V & Powell, DW 2006, 'Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa', Journal of Immunology, vol. 177, no. 9, pp. 5968-5979.
Saada JI, Pinchuk I, Barrera CA, Adegboyega PA, Suarez G, Mifflin RC et al. Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa. Journal of Immunology. 2006 Nov 1;177(9):5968-5979.
Saada, Jamal I. ; Pinchuk, Iryna ; Barrera, Carlos A. ; Adegboyega, Patrick A. ; Suarez, Giovanni ; Mifflin, Randy C. ; Di Mari, John F. ; Reyes, Victor ; Powell, Don W. / Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa. In: Journal of Immunology. 2006 ; Vol. 177, No. 9. pp. 5968-5979.
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