Gαi2-Deficient Mice with Colitis Exhibit a Local Increase in Memory CD4+ T Cells and Proinflammatory Th1-Type Cytokines

C. Elisabeth Hörnquist, Xiaohui Lu, Pamela M. Rogers-Fani, Uwe Rudolph, Scott Shappell, Lutz Birnbaumer, Gregory R. Harriman

Research output: Contribution to journalArticlepeer-review

Abstract

Mice with targeted deletion of the G protein Gαi2 develop an inflammatory bowel disease closely resembling ulcerative colitis. To better define disease pathogenesis, the mucosal immune system in Gαi2-deficient mice was studied. Phenotypic analysis of large intestine lamina propria lymphocytes revealed a large increase in memory CD4+ T cells (CD44high, CD45RBlow, CD62Llow). Furthermore, expression of the mucosal homing receptor integrin β7 was increased on mucosal, but not systemic, CD4+ T cells. Analysis of cytokine production revealed a marked increase in proinflammatory Th1-type cytokines in inflamed colons, as compared with wild-type mice or Gαi2-deficient mice without colitis. Thus, IFN-γ and IL-1β levels were increased 13-fold and 30-fold, respectively, with more modest increases in IL-6 levels (5-fold) and TNF levels (2-fold). Inflamed colons of Gαi2-deficient mice also demonstrated increased IL-12 p40 mRNA levels. No increase in IL-2, IL-4, IL-5, and IL-10 was seen. Large intestinal epithelial cells in Gαi2-deficient mice with colitis were found by immunohistochemistry to express increased Large intestinal epithelial cells in Gαi2-deficient mice with colitis were found by immunohistochemistry to express increased levels of both MHC class I and class II Ags. Colitis was associated with increased IgG levels (60-fold increase), predominantly IgG2a (135-fold increase), in large but not small intestinal secretions. This was shown by ELISPOT analysis to result from local production within the lamina propria.

Original languageEnglish (US)
Pages (from-to)1068-1077
Number of pages10
JournalJournal of Immunology
Volume158
Issue number3
StatePublished - Feb 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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