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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.
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Research Article Immunology

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

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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

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Figure 7

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

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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 © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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