Journal
JOURNAL OF IMMUNOLOGY
Volume 196, Issue 11, Pages 4750-4759Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1600235
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Funding
- Paivikki and Sakari Sohlberg Foundation
- Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research) [285503, 218057]
- Finnish Diabetes Research Foundation
- Maud Kuistila Memorial Fund
- Turku University Foundation
- Sigrid Juselius Foundation
- Finnish Microarray and Sequencing Centre (University of Turku and Abo Akademi University and Biocenter Finland Genome-Wide Methods Technology Platform)
- Academy of Finland (AKA) [285503, 218057, 285503, 218057] Funding Source: Academy of Finland (AKA)
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Dendritic cells (DCs) bear the main responsibility for initiation of adaptive immune responses necessary for antimicrobial immunity. In the small intestine, afferent lymphatics convey Ags and microbial signals to mesenteric lymph nodes (LNs) to induce adaptive immune responses against microbes and food Ags derived from the small intestine. Whether the large intestine is covered by the same lymphatic system or represents its own lymphoid compartment has not been studied until very recently. We identified three small mesenteric LNs, distinct from small intestinal LNs, which drain lymph specifically from the colon, and studied DC responses to the attaching and effacing pathogen Citrobacter rodentium in these. Transcriptional profiling of conventional (CD11c(high)CD103(high)) DC and plasmacytoid (plasmacytoid DC Ag-1(high)B220(+)CD11c(int)) DC (pDC) populations during steady-state conditions revealed activity of distinct sets of genes in these two DC subsets, both in small intestinal and colon-draining LNs. C. rodentium activated DC especially in colon-draining LNs, and gene expression changed in pDC more profoundly than in conventional DC. Among the genes most upregulated in pDC were C-type lectin receptor CLEC4E, IL-1Rs (IL-1R1 and -2), proinflammatory cytokines (IL-1a and IL-6), and TLR6. Our results indicate that colon immune surveillance is distinct from that of the small intestine in terms of draining LNs, and identify pDC as active sentinels of colonic inflammation and/or microbial dysbiosis.
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