Generation of colonic IgA-secreting cells in the caecal patch.
Gut-associated lymphoid tissues are responsible for the generation of IgA-secreting cells. However, the function of the caecal patch, a lymphoid tissue in the appendix, remains unknown. Here we analyse the role of the caecal patch using germ-free mice colonized with intestinal bacteria after appendectomy. Appendectomized mice show delayed accumulation of IgA(+) cells in the large intestine, but not the small intestine, after colonization. Decreased colonic IgA(+) cells correlate with altered faecal microbiota composition. Experiments using photoconvertible Kaede-expressing mice or adoptive transfer show that the caecal patch IgA(+) cells migrate to the large and small intestines, whereas Peyer's patch cells are preferentially recruited to the small intestine. IgA(+) cells in the caecal patch express higher levels of CCR10. Dendritic cells in the caecal patch, but not Peyer's patches, induce CCR10 on cocultured B cells. Thus, the caecal patch is a major site for generation of IgA-secreting cells that migrate to the large intestine.
1] Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan [2] Department of Pediatric Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Kazunori
K
Masahata
1] Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan [2] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
Eiji
E
Umemoto
1] Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan [2] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
Hisako
H
Kayama
Department of Immunology and Cell Biology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Manato
M
Kotani
Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Shota
S
Nakamura
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Takashi
T
Kurakawa
Department of Immunology and Cell Biology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Junichi
J
Kikuta
Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Kazuyoshi
K
Gotoh
Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Daisuke
D
Motooka
Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Shintaro
S
Sato
Department of Microbiology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
Tomonori
T
Higuchi
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Yoshihiro
Y
Baba
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Tomohiro
T
Kurosaki
1] Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan [2] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
Makoto
M
Kinoshita
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Yosuke
Y
Shimada
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Taishi
T
Kimura
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Ryu
R
Okumura
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Akira
A
Takeda
The Institute of Experimental Animal Sciences, Faculty of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Masaru
M
Tajima
Department of Microbiology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
Osamu
O
Yoshie
Department of Pediatric Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Masahiro
M
Fukuzawa
1] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan [2] Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Hiroshi
H
Kiyono
Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN, Yokohama 230-0045, Japan.
Sidonia
S
Fagarasan
1] Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan [2] Laboratory of Genomic Research on Pathogenic Bacteria, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Tetsuya
T
Iida
1] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan [2] Department of Immunology and Cell Biology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Masaru
M
Ishii
1] Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan [2] Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan.
Kiyoshi
K
Takeda
D019264:Adoptive Transfer; D000818:Animals; D001065:Appendix / Q000166:cytology* / Q000276:immunology*; D001483:Base Sequence; D002465:Cell Movement / Q000276:immunology*; D003106:Colon / Q000166:cytology*; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D005243:Feces / Q000382:microbiology; D005434:Flow Cytometry; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D064307:Microbiota / Q000235:genetics*; D008969:Molecular Sequence Data; D010581:Peyer's Patches / Q000166:cytology; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
D017931:DNA Primers; D007070:Immunoglobulin A; C513582:Kaede protein, Trachyphyllia geoffroyi; D008164:Luminescent Proteins; D012336:RNA, Ribosomal, 16S