Abstract
CD103(+) dendritic cells (DCs) are the major conventional DC population in the intestinal lamina propria (LP). Our previous report showed that a small number of cells in the LP could be classified into four subsets based on the difference in CD11c/CD11b expression patterns: CD11c(hi)CD11b(lo) DCs, CD11c(hi)CD11b(hi) DCs, CD11c(int)CD11b(int) macrophages, and CD11c(int)CD11b(hi) eosinophils. The CD11c(hi)CD11b(hi) DCs, which are CD103(+), specifically express TLR5 and induce the differentiation of naive B cells into IgA(+) plasma cells. These DCs also mediate the differentiation of Ag-specific Th17 and Th1 cells in response to flagellin. We found that small intestine CD103(+) DCs of the LP (LPDCs) could be divided into a small subset of CD8α(+) cells and a larger subset of CD8α(-) cells. Flow cytometry analysis revealed that CD103(+)CD8α(+) and CD103(+)CD8α(-) LPDCs were equivalent to CD11c(hi)CD11b(lo) and CD11c(hi)CD11b(hi) subsets, respectively. We analyzed a novel subset of CD8α(+) LPDCs to elucidate their immunological function. CD103(+)CD8α(+) LPDCs expressed TLR3, TLR7, and TLR9 and produced IL-6 and IL-12p40, but not TNF-α, IL-10, or IL-23, following TLR ligand stimulation. CD103(+)CD8α(+) LPDCs did not express the gene encoding retinoic acid-converting enzyme Raldh2 and were not involved in T cell-independent IgA synthesis or Foxp3(+) regulatory T cell induction. Furthermore, CD103(+)CD8α(+) LPDCs induced Ag-specific IgG in serum, a Th1 response, and CTL activity in vivo. Accordingly, CD103(+)CD8α(+) LPDCs exhibit a different function from CD103(+)CD8α(-) LPDCs in active immunity. This is the first analysis, to our knowledge, of CD8α(+) DCs in the LP of the small intestine.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / immunology
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Antigens, CD / metabolism
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CD8 Antigens / immunology
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CD8 Antigens / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Proliferation
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Cells, Cultured
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Cytotoxicity, Immunologic / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Flow Cytometry
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Forkhead Transcription Factors / immunology
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Forkhead Transcription Factors / metabolism
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Integrin alpha Chains / immunology
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Integrin alpha Chains / metabolism
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Interleukin-12 Subunit p40 / immunology
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Interleukin-12 Subunit p40 / metabolism
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism
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Intestine, Small / immunology*
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Intestine, Small / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Toll-Like Receptor 3 / genetics
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Toll-Like Receptor 3 / immunology
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Toll-Like Receptor 3 / metabolism
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Toll-Like Receptor 7 / genetics
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Toll-Like Receptor 7 / immunology
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Toll-Like Receptor 7 / metabolism
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Toll-Like Receptor 9 / genetics
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Toll-Like Receptor 9 / immunology
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Toll-Like Receptor 9 / metabolism
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Toll-Like Receptors / genetics
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Toll-Like Receptors / immunology*
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Toll-Like Receptors / metabolism
Substances
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Antigens, CD
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CD8 Antigens
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CD8 antigen, alpha chain
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Integrin alpha Chains
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Interleukin-12 Subunit p40
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Interleukin-6
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Toll-Like Receptor 3
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Toll-Like Receptor 7
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Toll-Like Receptor 9
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Toll-Like Receptors
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alpha E integrins