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

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)605-615
Number of pages11
JournalJournal of Clinical Investigation
Volume117
Issue number3
DOIs
Publication statusPublished - 01-03-2007

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Granuloma
Interleukin-4
Immunoglobulin G
Interleukin-23
Cell Differentiation
Theoretical Models
Macrophages
Inflammation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Mizoguchi, A., Ogawa, A., Takedatsu, H., Sugimoto, K., Shimomura, Y., Shirane, K., ... Bhan, A. K. (2007). Dependence of intestinal granuloma formation on unique myeloid DC-like cells. Journal of Clinical Investigation, 117(3), 605-615. https://doi.org/10.1172/JCI30150
Mizoguchi, Atsushi ; Ogawa, Atsushiro ; Takedatsu, Hidetoshi ; Sugimoto, Ken ; Shimomura, Yasuyo ; Shirane, Katsunori ; Nagahama, Kiyotaka ; Nagaishi, Takashi ; Mizoguchi, Emiko ; Blumberg, Richard S. ; Bhan, Atul K. / Dependence of intestinal granuloma formation on unique myeloid DC-like cells. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 3. pp. 605-615.
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Mizoguchi, A, Ogawa, A, Takedatsu, H, Sugimoto, K, Shimomura, Y, Shirane, K, Nagahama, K, Nagaishi, T, Mizoguchi, E, Blumberg, RS & Bhan, AK 2007, 'Dependence of intestinal granuloma formation on unique myeloid DC-like cells', Journal of Clinical Investigation, vol. 117, no. 3, pp. 605-615. https://doi.org/10.1172/JCI30150

Dependence of intestinal granuloma formation on unique myeloid DC-like cells. / Mizoguchi, Atsushi; Ogawa, Atsushiro; Takedatsu, Hidetoshi; Sugimoto, Ken; Shimomura, Yasuyo; Shirane, Katsunori; Nagahama, Kiyotaka; Nagaishi, Takashi; Mizoguchi, Emiko; Blumberg, Richard S.; Bhan, Atul K.

In: Journal of Clinical Investigation, Vol. 117, No. 3, 01.03.2007, p. 605-615.

Research output: Contribution to journalArticle

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AU - Shimomura, Yasuyo

AU - Shirane, Katsunori

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AU - Mizoguchi, Emiko

AU - Blumberg, Richard S.

AU - Bhan, Atul K.

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N2 - 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.

AB - 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.

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