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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 1

Development of intestinal inflammation–associated granulomas in the absence of IL-4 and B cells.

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Development of intestinal inflammation–associated granulomas in the abse...
(A–D) In αμIL4TKO mice (24 weeks of age), granulomas are detectable within the colonic mucosa (A) as well as in the ileocecal areas (B). In contrast, granulomas are undetectable in the age-matched WT (C) and αμDKO (D) mice. (E and F) Gross features of the large intestines of αμIL4TKO (E) and αμDKO (F) mice at 24 weeks of age are shown. The inflammation is mostly restricted to the ileocecal junction (arrow) and proximal colon in αμIL4TKO mice whereas the inflammation involves the entire colon, in particular the distal colon (arrowheads), in αμDKO mice. (G) RPA shows expression of proinflammatory cytokine (IL-1β) in the ileocecal junction of αμIL4TKO (αμIL4) but not αμDKO (αμ) mice (24 weeks of age). Data are representative of 2 individual experiments. (H) Frequency of colitis in WT (open squares, n = 168), TCRαKO (open circles, n = 222), αIL4DKO (open triangles, n = 144), αμDKO (closed circles, n = 218) and αμIL4TKO (closed triangles, n = 104) mice at various ages are shown. MIF, Macrophage migration inhibitory factor.

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

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