Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
J Immunol. 2011 Jun 1;186(11):6287-95. doi: 10.4049/jimmunol.1004036. Epub 2011 Apr 27.
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.
CD103(+)树突状细胞（DCs）是肠道固有层（LP）中主要的常规 DC 群体。我们之前的报告显示，LP 中的一小部分细胞可以根据 CD11c/CD11b 表达模式的差异分为四个亚群：CD11c(hi)CD11b(lo) DCs、CD11c(hi)CD11b(hi) DCs、CD11c(int)CD11b(int)巨噬细胞和 CD11c(int)CD11b(hi)嗜酸性粒细胞。CD11c(hi)CD11b(hi) DCs 是 CD103(+)，特异性表达 TLR5，并诱导初始 B 细胞分化为 IgA(+)浆细胞。这些 DC 还介导对鞭毛蛋白的抗原特异性 Th17 和 Th1 细胞的分化。我们发现，肠道 LP 的 CD103(+)DC（LPDC）可分为一小部分 CD8α(+)细胞和大部分 CD8α(-)细胞。流式细胞术分析显示，CD103(+)CD8α(+)和 CD103(+)CD8α(-)LPDC 分别相当于 CD11c(hi)CD11b(lo)和 CD11c(hi)CD11b(hi)亚群。我们分析了一个新型的 CD8α(+)LPDC 亚群，以阐明其免疫学功能。CD103(+)CD8α(+) LPDC 在 TLR 配体刺激后表达 TLR3、TLR7 和 TLR9，并产生 IL-6 和 IL-12p40，但不产生 TNF-α、IL-10 或 IL-23。CD103(+)CD8α(+) LPDC 不表达视黄酸转化酶 Raldh2 的基因，不参与 T 细胞非依赖性 IgA 合成或 Foxp3(+)调节性 T 细胞诱导。此外，CD103(+)CD8α(+) LPDC 在体内诱导抗原特异性 IgG 血清、Th1 反应和 CTL 活性。因此，与 CD103(+)CD8α(-)LPDC 相比，CD103(+)CD8α(+)LPDC 在主动免疫中表现出不同的功能。这是我们所知的，对小肠 LP 中 CD8α(+)DC 的首次分析。
