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Protection against colitis by CD100-dependent modulation of intraepithelial gamma delta T lymphocyte function

Academic Article
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Overview

related to degree

  • Komori-Occhicone, Heather Kiyomi, Ph.D. in Biology, Scripps Research 2002 - 2008

authors

  • Meehan, T. F.
  • Witherden, D. A.
  • Kim, C. H.
  • Sendaydiego, K.
  • Ye, I.
  • Garijo, O.
  • Komori-Occhicone, Heather Kiyomi
  • Kumanogoh, A.
  • Kikutani, H.
  • Eckmann, L.
  • Havran, Wendy

publication date

  • 2014

journal

  • Mucosal immunology  Journal

abstract

  • Intraepithelial γδ T lymphocytes (γδ IEL) have important roles in repair of tissue damage at epithelial sites, such as skin and intestine. Molecules that orchestrate these γδ T-cell functions are not well defined. Recently, interaction of the semaphorin CD100 on skin γδ T cells with plexin B2 on keratinocytes was shown to be important for effective γδ T-cell function in the epidermis, which raised the possibility that CD100 may exert similar functions in the intestinal tract. In this study, we find that CD100 is expressed on all IEL, and plexin B2 is present on all epithelial cells of the mouse colon. Using the dextran sulfate sodium (DSS) mouse model of colitis, disease severity is significantly exacerbated in CD100-deficient (CD100(-/-)) mice, with increased colon ulceration and mucosal infiltration with inflammatory cells. The severe colitis in CD100(-/-) mice is attributable to the failure of the colon epithelium to mount a proliferative response to damage. Unlike wild-type γδ IEL, γδ IEL from CD100(-/-) mice fail to produce keratinocyte growth factor-1 (KGF-1) in response to DSS treatment. Administration of recombinant KGF-1 to CD100(-/-) animals ameliorates disease and reverses colitis susceptibility. These results demonstrate that CD100-mediated signals are critical for effective activation of γδ IEL to produce growth factors, including KGF-1, that are required for healing of the colon epithelium during colitis.

subject areas

  • Animals
  • Antigens, CD
  • Colitis
  • Dextran Sulfate
  • Disease Models, Animal
  • Female
  • Fibroblast Growth Factor 7
  • Gene Expression
  • Genetic Predisposition to Disease
  • Intestinal Mucosa
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Semaphorins
  • T-Lymphocytes
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Identity

PubMed Central ID

  • PMC3795871

International Standard Serial Number (ISSN)

  • 1935-3456 (Electronic) 1933-0219 (Linking)

Digital Object Identifier (DOI)

  • 10.1038/mi.2013.32

PubMed ID

  • 23695512
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Additional Document Info

start page

  • 134

end page

  • 142

volume

  • 7

issue

  • 1

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