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Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10178-10183. doi: 10.1073/pnas.1712837114. Epub 2017 Sep 6.

Gallbladder-derived surfactant protein D regulates gut commensal bacteria for maintaining intestinal homeostasis.

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Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.
Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Laboratory of Metagenomics, Department of Computational Biology and Medical Science, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8561, Japan.
Department of Target Therapy Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Department of Immune Regulation, Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Max Planck-The University of Tokyo Center for Integrative Inflammology, Tokyo 153-8505, Japan.
Department of Pathobiology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 169-8555, Japan.
Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan;


The commensal microbiota within the gastrointestinal tract is essential in maintaining homeostasis. Indeed, dysregulation in the repertoire of microbiota can result in the development of intestinal immune-inflammatory diseases. Further, this immune regulation by gut microbiota is important systemically, impacting health and disease of organ systems beyond the local environment of the gut. What has not been explored is how distant organs might in turn shape the microbiota via microbe-targeted molecules. Here, we provide evidence that surfactant protein D (SP-D) synthesized in the gallbladder and delivered into intestinal lumen binds selectively to species of gut commensal bacteria. SP-D-deficient mice manifest intestinal dysbiosis and show a susceptibility to dextran sulfate sodium-induced colitis. Further, fecal transfer from SP-D-deficient mice to wild-type, germ-free mice conveyed colitis susceptibility. Interestingly, colitis caused a notable increase in Sftpd gene expression in the gallbladder, but not in the lung, via the activity of glucocorticoids produced in the liver. These findings describe a unique mechanism of interorgan regulation of intestinal immune homeostasis by SP-D with potential clinical implications such as cholecystectomy.


colitis; gallbladder; glucocorticoids; gut microbiota; surfactant protein D

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