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1 Purinergic signaling mediates mast cell activation in intestinal inflammation Yosuke Kurashima, Hiroshi Kiyono and Jun Kunisawa Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minatoku, Tokyo, Japan; Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Asagi Saito, Ibaraki, Osaka, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan - TNF IL- NOD WBBFkit-Kit w Kit w-v c-kit WBBF-Kit WW-v Kraneveld TNF WBBF-Kit WW-v T c-kit CBL-Kit W-shW-sh T CBL-Kit W-shW-sh c-kit DTDTR pp.

2 toxin receptor mediated conditional cell knock outtreck CBL-Kit W-shW-sh mast cell specific-treckmas-treck MaS-TRECK IL- HS IE DTR MaS-TRECK DT CBL-Kit W-shW-sh MaS-TRECK Kraneveld A CD A in vitro IgE A A A CD IgE L L IgE L T B CD F F ATP PX ATP Burnstock ATP purinergic hypothesis ATP PX PY ATP PX PX PX PX PX PX C ATP pore C pore ATP K efflux NLRP IL- IL- ATP ATP GVHD ATP ATP ATP T Th

3 Pannexin-Panx ConnexinConx ATP PX PY CDCD ADP-PY ATP ATP T Th ATP CDCD ATP PXF PXATP CD- CCL CXCL IL-IL-TNF CD PX ATP F PX PX PX PX ATP-PX PX PX PX ATP ATP CD CD ATP ATPADPAMP ATP AB A ATP ADP ATP

4 PX ATP ATP PX ATP ADPAMP ATP ATP ATP ADP PX ATP ADP ADP PX ADP ATP ATP Pannexin- Connexin ADP ADPATP ADPATP ATP diadenosine pentaphosphateadp UDP ADP ADP ATP ATP ADP ATP PX ATP ADP ATP PX ATP PX PX PX ATP Kaser, A., Zeissig, S., Blumberg, R.S.Annu. Rev. Immunol.,,. Kurashima, Y., Goto, Y., Kiyono, H.Eur. J. Immunol.,,. Hamilton, M.J., Sinnamon, M.J., Lyng, G.D., Glickman, J.N., Wang, X., Xing, W., Krilis, S.A., Blumberg, R.S., Adachi, R., Lee, D.M., Stevens, R.L. Proc. Natl. Acad. Sci. USA,,. Rijnierse, A., Redegeld, F.A., Blokhuis, B.R., Van der Heijden, M.W., Te Velde, A.A., Pronk, I., Hommes, D.W., Nijkamp, F. P., Koster, A.S., Kraneveld, A.D.J. Immunol.,,. Reber, L.L., Marichal, T., Galli, S.J.Trends Immunol.,,. Kurashima, Y., Amiya, T., Nochi, T., Fujisawa, K., Haraguchi, T., Iba, H., Tsutsui, H., Sato, S., Nakajima, S., Iijima, H., Kubo, M., Kunisawa, J., Kiyono, H.Nat. Commun.,,. doi:.ncomms. Idzko, M., Ferrari, D., Eltzschig, H.K.Nature.,,. Junger, W.G.Nat. Rev. Immunol.,,. Ochoa-Cortes, F., Liñán-Rico, A., Jacobson, K.A., Christofi, F.L.Inflamm. Bowel Dis.,,. Burnstock, G.Eur. J. Pharmacol.,,. Colgan, S.P. Eltzschig, H.K.Annu. Rev. Physiol.,,. Kurashima, Y. Kiyono, H.Exp. Mol. Med.,, e. doi:.emm.. Marques, C.C., Castelo-Branco, M.T., Pacheco, R.G., Buongusto, F., do Rosário, A. Jr., Schanaider, A., Coutinho-Silva, R., de, Souza, H.S.Biochim. Biophys. Acta,,

5 . Neves, A.R., Castelo-Branco, M.T., Figliuolo, V.R., Bernardazzi, C., Buongusto, F., Yoshimoto, A., Nanini, H.F., Coutinho, C.M., Carneiro, A.J., Coutinho-Silva, R., de Souza, H.S.Inflamm. Bowel Dis.,,. Kurashima, Y., Amiya, T., Fujisawa, K., Shibata, N., Suzuki, Y., Kogure, Y., Hashimoto, E., Otsuka, A., Kabashima, K., Sato, S., Sato, T., Kubo, M., Akira, S., Miyake, K., Kunisawa, J., Kiyono, H.Immunity,,. DCPD

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