CCR7 Is Critically Important for Migration of Dendritic Cells in Intestinal Lamina Propria to Mesenteric Lymph Nodes
Abstract
Although dendritic cells (DCs) located in the small intestinal lamina propria (LP-DCs) migrate to mesenteric lymph nodes (MLNs) constitutively, it is unclear which chemokines regulate their trafficking to MLNs. In this study we report that LP-DCs in unperturbed mice require CCR7 to migrate to MLNs. In vitro, LP-DCs expressing CCR7 migrated toward CCL21, although the LP-DCs appeared morphologically and phenotypically immature. In MLNs, DCs bearing the unique LP-DC phenotype (CD11chighCD8αintCD11blowαLlowβ7high and CD11chighCD8α−CD11bhighαLlowβ7high) were abundant in wild-type mice, but were markedly fewer in CCL19-, CCL21-Ser-deficient plt/plt mice and were almost absent in CCR7-deficient mice, indicating the critical importance of CCR7 in LP-DC trafficking to MLNs. Interestingly, CCR7+ DCs in MLNs with the unique LP-DC phenotype had numerous vacuoles containing cellular debris in the cytoplasm, although MLN-DCs themselves were poorly phagocytic, suggesting that the debris was derived from the LP, where the LP-DCs ingested apoptotic intestinal epithelial cells (IECs). Consistent with this, LP-DCs ingested IECs vigorously in vitro. By presenting IEC-associated Ag, the LP-DCs also induce T cells to produce IL-4 and IL-10. Collectively, these results strongly suggest that LP-DCs with unique immunomodulatory activities migrate to MLNs in a CCR7-dependent manner to engage in the presentation of IEC-associated Ags acquired in the LP.
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mRNA expression of Ccr7 was significantly lower in the colon of mice gavaged with Bacteroides.
“the mRNA expression of Ccr7, which is critically important for migration of antigen-presenting cells in the intestinal lamina propria to the mesenteric lymph nodes (MLNs), 44 was significantly lower in the colon of mice gavaged with Bacteroides (Figure VIA and VIB, Table III in the onlineonly Data Supplement).”
From <i>Bacteroides vulgatus</i> and <i>Bacteroides dorei</i> Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis (2018) · cites this paper as [44]
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- Authors
- Jang, M. H., Sougawa, N., Tanaka, T., Hirata, T., Hiroi, T., Tohya, K., Guo, Z., Umemoto, E., Ebisuno, Y., Yang, B.-G., Seoh, J.-Y., Lipp, M., Kiyono, H., & Miyasaka, M.
- Affiliations
- The University of Osaka (JP)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Department of Anatomy, Kansai College of Oriental Medicine , Osaka ,
- Ewha Womans University (KR)
- Max Delbrück Center (DE)
- Corresponding author
- Sougawa, Nagako
- Tanaka, Toshiyuki
- Guo, Zijin
- Umemoto, Eiji
- Ebisuno, Yukihiko
- Miyasaka, Masayuki
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-01
- Volume
- 176
- Issue
- 2
- Pages
- 803-810
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2164386060
- Cited by
- 430
- References
- 44
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 9 · 2023: 10 · 2022: 19 · 2021: 18 · 2020: 14 · 2019: 27 · 2018: 15 · 2017: 18 · 2016: 20 · 2015: 20 · 2014: 23 · 2013: 33 · 2012: 17
- FWCI
- 16.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- CCR7, dendritic cells, intestinal lamina propria, mesenteric lymph nodes, dendritic cell migration, CCL21, CCL19, chemokine signaling, phagocytosis, antigen presentation, IL-4, IL-10, immunomodulation, small intestine
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Cell Movement, Dendritic Cells, DNA, Endocytosis, Epithelial Cells, Intestinal Mucosa, Lymph Nodes, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, CD4-Positive T-Lymphocytes, Interleukin-4, Gene Expression, Interleukin-10, Apoptosis, Antigen Presentation, Mice, Knockout, Receptors, Chemokine, Chemokines, CC, Mice, Receptors, CCR7, Chemokine CCL21, In Vitro Techniques
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