Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. Export

@article{citeulike:2885089, abstract = {Intestinal macrophages play a central role in regulation of immune responses against commensal bacteria. In general, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines against commensal bacteria. In this study, we identified what we believe to be a unique macrophage subset in human intestine. This subset expressed both macrophage (CD14, CD33, CD68) and DC markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as IL-23, TNF-alpha, and IL-6, than typical intestinal resident macrophages (CD14(-)CD33(+) macrophages). In patients with Crohn disease (CD), the number of these CD14(+) macrophages were significantly increased compared with normal control subjects. In addition to increased numbers of cells, these cells also produced larger amounts of IL-23 and TNF-alpha compared with those in normal controls or patients with ulcerative colitis. In addition, the CD14(+) macrophages contributed to IFN-gamma production rather than IL-17 production by lamina propria mononuclear cells (LPMCs) dependent on IL-23 and TNF-alpha. Furthermore, the IFN-gamma produced by LPMCs triggered further abnormal macrophage differentiation with an IL-23-hyperproducing phenotype. Collectively, these data suggest that this IL-23/IFN-gamma-positive feedback loop induced by abnormal intestinal macrophages contributes to the pathogenesis of chronic intestinal inflammation in patients with CD.}, address = {Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. Department of Surgery, Yokohama City Hospital, Yokohama, Japan. Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.}, author = {Kamada, Nobuhiko and Hisamatsu, Tadakazu and Okamoto, Susumu and Chinen, Hiroshi and Kobayashi, Taku and Sato, Toshiro and Sakuraba, Atsushi and Kitazume, Mina T T. and Sugita, Akira and Koganei, Kazutaka and Akagawa, Kiyoko S S. and Hibi, Toshifumi}, citeulike-article-id = {2885089}, citeulike-linkout-0 = {http://dx.doi.org/10.1172/JCI34610}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18497880}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18497880}, day = {2}, doi = {10.1172/JCI34610}, issn = {0021-9738}, journal = {The Journal of clinical investigation}, keywords = {cd14, crohn, macrophage}, month = {June}, number = {6}, pages = {2269--2280}, posted-at = {2008-06-12 03:48:20}, priority = {2}, title = {Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis.}, url = {http://dx.doi.org/10.1172/JCI34610}, volume = {118}, year = {2008} }

TY - JOUR ID - citeulike:2885089 L3 - citeulike-article-id:2885089 N2 - Intestinal macrophages play a central role in regulation of immune responses against commensal bacteria. In general, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines against commensal bacteria. In this study, we identified what we believe to be a unique macrophage subset in human intestine. This subset expressed both macrophage (CD14, CD33, CD68) and DC markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as IL-23, TNF-alpha, and IL-6, than typical intestinal resident macrophages (CD14(-)CD33(+) macrophages). In patients with Crohn disease (CD), the number of these CD14(+) macrophages were significantly increased compared with normal control subjects. In addition to increased numbers of cells, these cells also produced larger amounts of IL-23 and TNF-alpha compared with those in normal controls or patients with ulcerative colitis. In addition, the CD14(+) macrophages contributed to IFN-gamma production rather than IL-17 production by lamina propria mononuclear cells (LPMCs) dependent on IL-23 and TNF-alpha. Furthermore, the IFN-gamma produced by LPMCs triggered further abnormal macrophage differentiation with an IL-23-hyperproducing phenotype. Collectively, these data suggest that this IL-23/IFN-gamma-positive feedback loop induced by abnormal intestinal macrophages contributes to the pathogenesis of chronic intestinal inflammation in patients with CD. IS - 6 JF - The Journal of clinical investigation SN - 0021-9738 AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. Department of Surgery, Yokohama City Hospital, Yokohama, Japan. Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan. EP - 2280 TI - Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. VL - 118 SP - 2269 KW - cd14 KW - crohn KW - macrophage AU - Kamada, Nobuhiko AU - Hisamatsu, Tadakazu AU - Okamoto, Susumu AU - Chinen, Hiroshi AU - Kobayashi, Taku AU - Sato, Toshiro AU - Sakuraba, Atsushi AU - Kitazume, Mina T AU - Sugita, Akira AU - Koganei, Kazutaka AU - Akagawa, Kiyoko S AU - Hibi, Toshifumi PY - 2008/06/02/ UR - http://dx.doi.org/10.1172/JCI34610 ER -