Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Dependence of intestinal granuloma formation on unique myeloid DC-like cells
Atsushi Mizoguchi, … , Richard S. Blumberg, Atul K. Bhan
Atsushi Mizoguchi, … , Richard S. Blumberg, Atul K. Bhan
Published March 1, 2007
Citation Information: J Clin Invest. 2007;117(3):605-615. https://doi.org/10.1172/JCI30150.
View: Text | PDF
Research Article Immunology

Dependence of intestinal granuloma formation on unique myeloid DC-like cells

  • Text
  • PDF
Abstract

Granulomas represent a localized inflammatory reaction that is characteristically observed in many inflammatory conditions. However, the mechanisms of granuloma formation have not been fully defined. Herein we demonstrate, by using experimental models of intestinal inflammation, that a unique CD11c+ DC-like cell subset that exhibits phenotypic and functional features of immature myeloid DCs and is characterized by the expression of a macrophage marker (F4/80) produces large amounts of IL-23 and directly induces the development of granulomas under a Th1-predominant intestinal inflammatory condition. Importantly, both IL-4 and IgG contribute to the suppression of F4/80+ DC-like cell–mediated granuloma formation by regulating the function and differentiation of this cell subset. In addition, enteric flora is required for the F4/80+ DC-like cell–mediated granuloma formation. Collectively, our data provide what we believe are novel insights into the involvement of F4/80+ DC-like cells in intestinal granuloma formation and demonstrate the role of host (IL-4 and IgG) and environmental (enteric flora) factors that regulate this function.

Authors

Atsushi Mizoguchi, Atsushiro Ogawa, Hidetoshi Takedatsu, Ken Sugimoto, Yasuyo Shimomura, Katsunori Shirane, Kiyotaka Nagahama, Takashi Nagaishi, Emiko Mizoguchi, Richard S. Blumberg, Atul K. Bhan

×

Figure 8

Potential ability of immature DCs to differentiate IMD-like cells capable of inducing granuloma formation.

Options: View larger image (or click on image) Download as PowerPoint
Potential ability of immature DCs to differentiate IMD-like cells capabl...
(A–D) BM-derived DCs from WT mice were expanded in in vitro culture with GM-CSF in the presence or absence of LPS. After culture, immature (CD11c+CD11b+CD86–, purity of more than 98%) (A, C, and D) and mature (CD11c+CD11b+CD86high, purity of more than 98%) (B) myeloid DCs were purified by FACS sorting. We directly injected 3 × 105 cells into the ileocecal junction of young αμIL4TKO (A and B), αIL4DKO (C), and αμDKO (D) mice (9 weeks of age). Recipient mice were sacrificed 3 weeks after injection. (E) Results of these local cell transfer experiments are summarized. Frequencies of granuloma induction are indicated on the bottom line. Red star indicates the tissues in which granuloma formation was induced. (F) BM-derived DCs from GFP transgenic mice were expanded in culture with GM-CSF in vitro. After culture, CD11c+ cells were purified through the MACS system. We injected 3 × 105 cells directly into the ileocecal junction of αμIL4TKO mice, and recipient mice were sacrificed 3 weeks after injection. Cells were isolated from the ileocecal junction and subjected to flow cytometric analysis. Top panel shows F4/80 expression on gated GFP+CD11c+ cells before cell injection (blue line) and from the recipient ileocecal junction (red line). F4/80 versus CD11c expression on gated GFP+ cells among the cells isolated from the recipient ileocecal junction is shown (bottom panel). Data are representative of 2 individual experiments.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts