Small Intestine Peyer’s Patches Are Major Induction Sites of the Helicobacter-Induced Host Immune Responses
2008; Elsevier BV; Volume: 134; Issue: 2 Linguagem: Inglês
10.1053/j.gastro.2007.12.007
ISSN1528-0012
AutoresNorihiko Watanabe, Keiichi Kiriya, Tsutomu Chiba,
Tópico(s)Immune Cell Function and Interaction
ResumoWe read with great interest the selected summary by Gewirtz et al1Gewirtz A.T. Sitaraman S.V. In"sight" into immune blindness: Helicobacter pylori-induced gastritis requires T cells primed in the small intestine Peyer's patches.Gastroenterology. 2007; 133: 1044-1045Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar in the September 2007 issue of Gastroenterology, which focuses on a recent paper by Nagai et al.2Nagai S. Mimuro H. Yamada T. et al.Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis.Proc Natl Acad Sci U S A. 2007; 104: 8971-8976Crossref PubMed Scopus (98) Google Scholar We have published a paper entitled "Essential role of Peyer's patches in the development of Helicobacter-induced gastritis," in the April 2007 issue of International Immunology,3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar in which we concluded that Peyer's patches (PPs) are required for the development of Helicobacter-induced gastritis. In our paper, we generated PP-null mice that develop well-organized lymphoid organs except for PPs3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar, 4Murai M. Yoneyama H. Ezaki T. et al.Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction.Nat Immunol. 2003; 4: 154-160Crossref PubMed Scopus (245) Google Scholar, 5Yoshida H. Honda K. Shikura R. et al.IL-7 receptor a+ CD3- cells in the embryonic intestine induces the organizing center of Peyer's patches.Int Immunol. 1999; 11: 643-655Crossref PubMed Scopus (255) Google Scholar, 6Hamada H. Hiroi T. Nishiyama Y. et al.Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine.J Immunol. 2002; 168: 57-64Crossref PubMed Scopus (376) Google Scholar and intragastrically infected the PP-null mice with Helicobacter felis.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar It has been reported that H felis infection in C57BL/6 mice induces chronic active gastritis that mimics the pathologic features observed in H pylori-induced gastritis in humans7Lee A. Fox J.G. Otto G. et al.A small animal model of human Helicobacter pylori active chronic gastritis.Gastroenterology. 1990; 99: 1315-1323Abstract PubMed Google Scholar, 8Ohana M. Okazaki K. Oshima C. et al.A critical role for IL-7R signaling in the development of Helicobacter felis-induced gastritis in mice.Gastroenterology. 2001; 121: 329-336Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar and results in the development of gastric cancer.9Fox J.G. Sheppard B.J. Dangler C.A. et al.Germ-line p53-targeted disruption inhibits Helicobacter-induced premalignant lesions and invasive gastric carcinoma through down-regulation of Th1 proinflammatory responses.Cancer Res. 2002; 62: 696-702PubMed Google Scholar We found that PP deficiency severely impaired both the development of Helicobacter-induced gastritis mediated by interferon (IFN)-γ–producing CD4+ T cells and the production of anti-Helicobacter antibodies despite marked bacterial colonization in the gastric mucosa.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar Thus, the data by Nagai et al and our data suggest that PPs have an important role not only in the cell-mediated immunity, but also in the specific humoral immunity against Helicobacter.In the Selected Summary,1Gewirtz A.T. Sitaraman S.V. In"sight" into immune blindness: Helicobacter pylori-induced gastritis requires T cells primed in the small intestine Peyer's patches.Gastroenterology. 2007; 133: 1044-1045Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Gewirtz and Sitaraman raised certain questions. What signals drive the priming of CD4+ T cells in PPs, and what direct these cells to migrate to the stomach and then to the site of infection? Nagai et al and we have demonstrated that Helicobacter antigens are taken up by dendritic cells (DCs) in PPs.2Nagai S. Mimuro H. Yamada T. et al.Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis.Proc Natl Acad Sci U S A. 2007; 104: 8971-8976Crossref PubMed Scopus (98) Google Scholar, 3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar It has been reported that DCs in PPs instruct naïve T cells to differentiate into gut-homing T cells that express gut-homing chemokine receptors, such as integrin α4β7, and CC chemokine receptor 9 (CCR9).10More J.R. Bono M.R. Manjunath N. et al.Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells.Nature. 2003; 424: 88-93Crossref PubMed Scopus (894) Google Scholar Indeed, we demonstrated that PP deficiency impairs differentiation of Helicobacter-specific IFN-γ–producing CD4+ T cells into CCR9-expressing cells.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar Furthermore, by transfer of splenic T cells from normal mice infected with Helicobacter into immunodeficient RAG2 knockout mice, we found that infiltration of Helicobacter-specific CD4+ T cells into the gastric mucosa depends on Helicobacter colonization in the stomach.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar Finally, we showed the expression of CCR9-ligand, TECK/CCL25 in Helicobacter-induced inflamed gastric mucosa.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar From these data, it is tempting to speculate that DCs in PPs taking up Helicobacter antigens prime CD4+ T cells to differentiate into Helicobacter-specific CD4+ T cells expressing gut-homing chemokine receptors, and interaction between bacteria and epithelial cells in the gastric mucosa triggers the recruitment of Helicobacter-specific CD4+ T cells that express gut-homing chemokine receptors into the infection sites. We read with great interest the selected summary by Gewirtz et al1Gewirtz A.T. Sitaraman S.V. In"sight" into immune blindness: Helicobacter pylori-induced gastritis requires T cells primed in the small intestine Peyer's patches.Gastroenterology. 2007; 133: 1044-1045Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar in the September 2007 issue of Gastroenterology, which focuses on a recent paper by Nagai et al.2Nagai S. Mimuro H. Yamada T. et al.Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis.Proc Natl Acad Sci U S A. 2007; 104: 8971-8976Crossref PubMed Scopus (98) Google Scholar We have published a paper entitled "Essential role of Peyer's patches in the development of Helicobacter-induced gastritis," in the April 2007 issue of International Immunology,3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar in which we concluded that Peyer's patches (PPs) are required for the development of Helicobacter-induced gastritis. In our paper, we generated PP-null mice that develop well-organized lymphoid organs except for PPs3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar, 4Murai M. Yoneyama H. Ezaki T. et al.Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction.Nat Immunol. 2003; 4: 154-160Crossref PubMed Scopus (245) Google Scholar, 5Yoshida H. Honda K. Shikura R. et al.IL-7 receptor a+ CD3- cells in the embryonic intestine induces the organizing center of Peyer's patches.Int Immunol. 1999; 11: 643-655Crossref PubMed Scopus (255) Google Scholar, 6Hamada H. Hiroi T. Nishiyama Y. et al.Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine.J Immunol. 2002; 168: 57-64Crossref PubMed Scopus (376) Google Scholar and intragastrically infected the PP-null mice with Helicobacter felis.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar It has been reported that H felis infection in C57BL/6 mice induces chronic active gastritis that mimics the pathologic features observed in H pylori-induced gastritis in humans7Lee A. Fox J.G. Otto G. et al.A small animal model of human Helicobacter pylori active chronic gastritis.Gastroenterology. 1990; 99: 1315-1323Abstract PubMed Google Scholar, 8Ohana M. Okazaki K. Oshima C. et al.A critical role for IL-7R signaling in the development of Helicobacter felis-induced gastritis in mice.Gastroenterology. 2001; 121: 329-336Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar and results in the development of gastric cancer.9Fox J.G. Sheppard B.J. Dangler C.A. et al.Germ-line p53-targeted disruption inhibits Helicobacter-induced premalignant lesions and invasive gastric carcinoma through down-regulation of Th1 proinflammatory responses.Cancer Res. 2002; 62: 696-702PubMed Google Scholar We found that PP deficiency severely impaired both the development of Helicobacter-induced gastritis mediated by interferon (IFN)-γ–producing CD4+ T cells and the production of anti-Helicobacter antibodies despite marked bacterial colonization in the gastric mucosa.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar Thus, the data by Nagai et al and our data suggest that PPs have an important role not only in the cell-mediated immunity, but also in the specific humoral immunity against Helicobacter. In the Selected Summary,1Gewirtz A.T. Sitaraman S.V. In"sight" into immune blindness: Helicobacter pylori-induced gastritis requires T cells primed in the small intestine Peyer's patches.Gastroenterology. 2007; 133: 1044-1045Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Gewirtz and Sitaraman raised certain questions. What signals drive the priming of CD4+ T cells in PPs, and what direct these cells to migrate to the stomach and then to the site of infection? Nagai et al and we have demonstrated that Helicobacter antigens are taken up by dendritic cells (DCs) in PPs.2Nagai S. Mimuro H. Yamada T. et al.Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis.Proc Natl Acad Sci U S A. 2007; 104: 8971-8976Crossref PubMed Scopus (98) Google Scholar, 3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar It has been reported that DCs in PPs instruct naïve T cells to differentiate into gut-homing T cells that express gut-homing chemokine receptors, such as integrin α4β7, and CC chemokine receptor 9 (CCR9).10More J.R. Bono M.R. Manjunath N. et al.Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells.Nature. 2003; 424: 88-93Crossref PubMed Scopus (894) Google Scholar Indeed, we demonstrated that PP deficiency impairs differentiation of Helicobacter-specific IFN-γ–producing CD4+ T cells into CCR9-expressing cells.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar Furthermore, by transfer of splenic T cells from normal mice infected with Helicobacter into immunodeficient RAG2 knockout mice, we found that infiltration of Helicobacter-specific CD4+ T cells into the gastric mucosa depends on Helicobacter colonization in the stomach.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar Finally, we showed the expression of CCR9-ligand, TECK/CCL25 in Helicobacter-induced inflamed gastric mucosa.3Kiriya K. Watanabe N. Nishio A. et al.Essential role of Peyer's patches in the development of Helicobacter-induced gastritis.Int Immunol. 2007; 19: 435-446Crossref PubMed Scopus (38) Google Scholar From these data, it is tempting to speculate that DCs in PPs taking up Helicobacter antigens prime CD4+ T cells to differentiate into Helicobacter-specific CD4+ T cells expressing gut-homing chemokine receptors, and interaction between bacteria and epithelial cells in the gastric mucosa triggers the recruitment of Helicobacter-specific CD4+ T cells that express gut-homing chemokine receptors into the infection sites. In"Sight" Into Immune Blindness: Helicobacter pylori–Induced Gastritis Requires T Cells Primed in the Small Intestine Peyer's PatchesGastroenterologyVol. 133Issue 3PreviewNagai S, Mimuro H, Yamada T, et al. (Departments of Microbiology and Immunology and Pathology, Keio University School of Medicine, Tokyo, Japan.) Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis. Proc Natl Acad Sci U S A 2007;104:8971–8976. Full-Text PDF
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