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
    • ASCI Milestone Awards
    • Video Abstracts
    • Conversations with Giants in Medicine
  • Reviews
    • View all reviews ...
    • The cGAS-STING pathway: DNA sensing in health and disease (Jun 2026)
    • Neurodegeneration (Mar 2026)
    • Clinical innovation and scientific progress in GLP-1 medicine (Nov 2025)
    • 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)
    • 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
  • ASCI Milestone Awards
  • Video Abstracts
  • Conversations with Giants in Medicine
  • 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, Atsushiro Ogawa, Hidetoshi Takedatsu, Ken Sugimoto, Yasuyo Shimomura, Katsunori Shirane, Kiyotaka Nagahama, Takashi Nagaishi, Emiko Mizoguchi, Richard S. Blumberg, Atul K. Bhan
Atsushi Mizoguchi, Atsushiro Ogawa, Hidetoshi Takedatsu, Ken Sugimoto, Yasuyo Shimomura, Katsunori Shirane, Kiyotaka Nagahama, Takashi Nagaishi, Emiko Mizoguchi, Richard S. Blumberg, Atul K. Bhan
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 7

Both IL-4 and IgG are required for the regulation of IMD-like cell–mediated granuloma formation.

Options: View larger image (or click on image) Download as PowerPoint
Both IL-4 and IgG are required for the regulation of IMD-like cell–media...
(A–E) CD11c+ cells from granulomatous of old αμIL4TKO mice were injected into the intestinal wall at the ileocecal junction in young αμIL4TKO mice. IL-4 (A, n = 5) or PBS (B, n = 5), or IgG from TCRαKO mice (C, n = 5) or WT mice (D, n = 5), were administered into recipient mice. Recipient mice were sacrificed at 3 weeks after local cell transfer. Scores of granulomas are summarized in E. Statistical significance is indicated by asterisks. *P < 0.05; **P < 0.0001. (F) RNA isolated from ileocecal junction of recipient mice with administration of PBS (black line, n = 5), IL-4 (red line, n = 5), or IgG (blue line, n = 5) was subjected to QPCR analysis for the detection of β-actin, IL-12p40, and p19. Lines represent the averages of 5 mice in each group. (G) Purified CD11c+ cells from granulomas of old αμIL4TKO mice were injected into the intestinal wall at the ileocecal junction in young αμIL4TKO mice without (top panels) or with (bottom panels) depletion of enteric bacteria by treatment with a combination of antibiotics. No granulomas were detectable in the decontaminated recipient mice (n = 8). Gross findings (left panels) show no recognizable nodular formation in the ileocecal junction with enlargement of cecum in the mouse with depleted enteric flora (bottom left) versus presence of granuloma formation in the ileocecal junction (arrow) without enlargement in the control mouse with enteric flora (top left).

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts