A new subset of CD103+CD8α+ DCs in the small intestine express TLR3, TLR7 and TLR9, and induce Th1 response and CTL activity
Kosuke Fujimoto, Thangaraj Karuppuchamy, Naoki Takemura, Masaki Shimohigoshi, Tomohisa Machida, Yasunari Haseda, Taiki Aoshi, Ken J. Ishii, Shizuo Akira and Satoshi Uematsu
CD103+ dendritic cells (DCs) are the major conventional DC population in the intestinal lamina propria (LP). Our previous report showed that low density cells in the LP could be classified into four subsets based on the difference in CD11c/CD11b expression patterns: CD11chiCD11blo DCs, CD11chiCD11bhi DCs, CD11cintCD11bint macrophages and CD11cintCD11bhi eosinophils. The CD11chiCD11bhi DCs, which are CD103+, specifically express TLR5 and induce the differentiation of naïve 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 CD11chiCD11blo and CD11chiCD11bhi 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 of CD8α+ DCs in the LP of the small intestine.