A New Subset of CD103(+)CD8 alpha(+) Dendritic Cells in the Small Intestine Expresses TLR3, TLR7, and TLR9 and Induces Th1 Response and CTL Activity

作者：Fujimoto Kosuke; Karuppuchamy Thangaraj; Takemura Naoki; Shimohigoshi Masaki; Machida Tomohisa; Haseda Yasunari; Aoshi Taiki; Ishii Ken J; Akira Shizuo; Uematsu Satoshi^*

来源：The Journal of Immunology, 2011, 186(11): 6287-6295.

DOI：10.4049/jimmunol.1004036

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 CD8 alpha(+) cells and a larger subset of CD8 alpha(-) cells. Flow cytometry analysis revealed that CD103(+)CD8 alpha(+) and CD103(+)CD8 alpha(-) LPDCs were equivalent to CD11c(hi) CD11b(lo) and CD11c(hi)CD11b(hi) subsets, respectively. We analyzed a novel subset of CD8 alpha(+) LPDCs to elucidate their immunological function. CD103(+)CD8 alpha(+) LPDCs expressed TLR3, TLR7, and TLR9 and produced IL-6 and IL-12p40, but not TNF-alpha, IL-10, or IL-23, following TLR ligand stimulation. CD103(+)CD8 alpha(+) 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(+)CD8 alpha(+) LPDCs induced Ag-specific IgG in serum, a Th1 response, and CTL activity in vivo. Accordingly, CD103(+)CD8 alpha(+) LPDCs exhibit a different function from CD103(+)CD8 alpha(-) LPDCs in active immunity. This is the first analysis, to our knowledge, of CD8 alpha(+) DCs in the LP of the small intestine. The Journal of Immunology, 2011, 186: 6287-6295.

• 出版日期2011-6-1