Mucosal Immunology

Prof. Ichiro Takahashi

【Members】
Professor; Ichiro Takahashi, DDS, PhD
Associate Professor; Kei Tobiume, DDS, PhD

【Research Keyword】
mucosal immunity, inflammation, host-microbe symbiosis

【Recent highlights】
Interactions between the microbiota and the mucosal immune system are absolutely important in shaping mucosal immune responses. It is becoming clear that specific microbes influence specific lymphoid and non-lymphoid populations, for example commensal bacteria survive within dendritic cells in Peyer’s patches and enhance mucosal IgA responses. We showed that Stenotrophomonas maltophilia is constitutively present in vivo in colonic lamina propria macrophages but not in lymphoid-tissue resident macrophages. Clinically isolated S. maltophilia enter bone marrow-derived macrophages (BMDMs) in vitro and persistent colonization increases mitochondrial respiration and IL-10 production. Colonization by S. maltophilia is impaired by IL-10 deficiency. The bacteria secrete a 25-KDa protein encoded by smlt2713. Expression of smlt2713 in BMDMs induces IL-10 production. Bacteria deficient in smlt2713 show reduced colonization and IL-10 production. In vivo, pre-transfer of smlt2713-transduced BMDMs protects against chronic enterocolitis. We thus identify a novel symbiotic network between commensal bacteria and colonic macrophages.

Profiles of Faculty and Research Scholars

【Education】
“Immunity” is defined as our body’s resistance against infectious and inflammatory diseases. The collection of molecules and cells/tissues that participate in the “host defense” is “the immune system”, and the coordinated reaction of these molecules/cells against not only harmful but also innocuous foreign materials is “the immune response”. We lecture as well as perform laboratory work concerning the immune system and response.
We show the importance of immunology for the progress of introducing examples of translational research from bench to bedside (e.g., immune therapy for tumors using newly discovered immunity-related rheostat molecules).
The goal of our undergraduate education at dental school is:
1. Increased participation learning of medically important immunology.
2. Increased basic knowledge of the immunological issues in health and disease.
3. Comprehension to develop diagnosis in medically crucial situations.

【Research】
We are determining (1) how a member of plant rhizosphere microbiota (Stenotrophomonas maltophilia) creates and regulates a physiologic
inflammation in gastrointestinal tissues; (2) how environmental bacteria cohabit in the intestinal mucosa, especially with in tissue resident macrophages; and (3) How the rhizosphere bacteria regulate / prevent pathologic inflammation in the gut. This work is supported by grant from the core research for evolutional science and technology (CREST) program of the Japan Science and Technology Agency.

【Featured publications】
1.    Persistent colonization of non-lymphoid tissue-resident macrophages by Stenotrophomonas maltophilia. Takahashi I, Hosomi K, Nagatake T, Tobou H, Yamamoto D, Hayashi I, Kurashima Y, Sato S, Shibata N, Goto Y, Maruyama F, Nakagawa I, Kuwae A, Abe A, Kunisawa J, Kiyono H. Int. Immunol. (2020) 32:133-141. 
2.    Mucosal regulatory cells in the gastrointestinal tract and periodontium. Takahashi I, Fujihashi K, Kiyono H. Periodontol. 2000. (2010) 54: 247-56. 
3.    New horizon of mucosal immunity and vaccines. Takahashi I, Nochi T, Yuki Y, Kiyono H. Curr. Opin. Immunol. (2009) 21: 352-8. 
4.    Intraepithelial lymphocytes: their shared and divergent immunological behaviors in the small and large intestine. Kunisawa J, Takahashi I, Kiyono H. Immunol. Rev. (2007) 215: 136-53.
5.    Colitis in mice lacking the common cytokine receptor g-chain is mediated by IL-6-producing CD4+ T cells. Kai Y, Takahashi I, Ishikawa H, Hiroi T, Mizushima T, Matsuda C, Kishi D, Hamada H, Tamagawa H, Ito T, Yoshizaki K, Kishimoto T, Matsuda H, Kiyono H. Gastroenterology (2005) 128: 922-34.
6.    Clonal expansion of double-positive intraepithelial lymphocytes by MHC class I-related chain A expressed in mouse small intestinal epithelium. Park EJ, Takahashi I, Ikeda J, Kawahara K, Okamoto T, Kweon MN, Fukuyama S, Groh V, Spies T, Obata Y, Miyazaki J, Kiyono H. J. Immunol. (2003) 171: 4131-9.


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