Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine

By A. Iwasaki, B. Kelsall. Journal of Experimental Medicine, 2000

640 citations recorded by the source corpus.

We describe the anatomical localization of three distinct dendritic cell (DC) subsets in the murine Peyer's patch (PP) and explore the role of chemokines in their recruitment. By two-color in situ immunofluorescence, CD11b+ myeloid DCs were determined to be present in the subepithelial dome (SED) region, whereas CD8α+ lymphoid DCs are present in the T cell–rich interfollicular region (IFR). DCs that lack expression of CD8α or CD11b (double negative) are present in both the SED and IFR. By in situ hybridization, macrophage inflammatory protein (MIP)-3α mRNA was dramatically expressed only by the follicle-associated epithelium overlying the SED, while its receptor, CCR6, was concentrated in the SED. In contrast, CCR7 was expressed predominantly in the IFR. Consistent with these findings, reverse transcriptase polymerase chain reaction analysis and in vitro chemotaxis assays using freshly isolated DCs revealed that CCR6 was functionally expressed only by DC subsets present in the SED, while all subsets expressed functional CCR7. Moreover, none of the splenic DC subsets migrated toward MIP-3α. These data support a distinct role for MIP-3α/CCR6 in recruitment of CD11b+ DCs toward the mucosal surfaces and for MIP-3β/CCR7 in attraction of CD8α+ DCs to the T cell regions. Finally, we demonstrated that all DC subsets expressed an immature phenotype when freshly isolated and maintained expression of subset markers upon maturation in vitro. In contrast, CCR7 expression by myeloid PP DCs was enhanced with maturation in vitro. In addition, this subset disappeared from the SED and appeared in the IFR after microbial stimulation in vivo, suggesting that immature myeloid SED DCs capture antigens and migrate to IFR to initiate T cell responses after mucosal microbial infections.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/8f7841ef28aed3c5c2be01f98fe5c9d467cf5254

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In Immunology

1. A. Iwasaki
2. B. Kelsall
3. H. Hemmi
4. R. Steinman
5. Shizuo Akira
6. R. Medzhitov
7. Taro Kawai
8. Jacques Banchereau

Citations in the corpus

• Dendritic cells: translating innate to adaptive immunity. (2006, background): “inflamed epithelia, an important interaction is the chemokine CCL20/MIP-1α made by the epithelium and the chemokine receptor CCR6 on the DCs [40, 44].”
• Development and function of dendritic cell subsets. (2014, neutral): “, the CCR6-CCL20 axis controlling migration toward the mucosal surfaces, whereas the CCR7-CCL19 axis is important for CD8 DC localization to the T cell region (Iwasaki and Kelsall, 2000).”
• Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells1 (2001, methodology): “DCs were prepared from spleen (SP) and PP, as previously described (5).”