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

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 3

Granuloma-associated CD11c+ cells exhibit a unique IMD-like phenotype with F4/80 expression.

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Granuloma-associated CD11c+ cells exhibit a unique IMD-like phenotype wi...
(A) Staining of CD11c versus CD11b (left panel) and B220 or CD8α expression (solid red histograms, right panels) on gated CD11b+CD11c+ cells from grossly recognizable granulomas (n = 12) are shown. (B) Expression (n = 9) of F4/80 or MOMA-1 on gated CD11b+CD11c+ cells are shown as solid green histograms. Black lines represent isotype control staining. (C) QPCR shows F4/80 expression by purified CD11c+ cells (n = 3) from granulomas and splenic CD4+ cells (n = 3). (D) Morphology of FACS-purified F4/80+CD11c+ cells from granulomas is shown. Fine dendrites are recognized on these cells (arrows). (E) Expressions of CD86 on granuloma-derived CD11c+CD11b+ cells (solid orange histograms) and BM-derived mature DCs (blue line) are shown. Black line represents isotype control staining. The averages of CD86 mean fluorescent intensity (MFI) on BM-derived immature (iDC, n = 3) and mature (mDC, n = 3) and granuloma-derived CD11c+CD11b+ cells (gDC, n = 10) are summarized. (F) T cells (T) from BALB/c mice were cultured without or with C57BL/6 mDC or gDC (n = 3) for 80 hours and pulsed with 1 μCi 3H for 16 hours. (G) iDC (n = 3), mDC (n = 3), and gDC (n = 3) were cultured with FITC-dextran at 4°C or 37°C and subjected to flow cytometric analysis. The averages of phagocytic activity are indicated as FITC-dextran MFI at 37°C minus FITC-dextran MFI at 4°C. Bottom panel shows gDC cultured with FITC-dextran at 37°C. Statistical significances are indicated by asterisks. **P < 0.001; *P < 0.05.