Temporal regulation of interleukin-12p70 (IL-12p70) and IL-12-related cytokines in splenic dendritic cell subsets during Leishmania donovani infection
Temporal regulation of interleukin-12p70 (IL-12p70) and IL-12-related cytokines in splenic dendritic cell subsets during Leishmania donovani infection
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DOI：
10.1128/iai.00643-07
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发表时间：
2008-01-01
影响因子：
3.1
通讯作者：
Kaye, Paul M.
中科院分区：
文献类型：
--
作者：
Maroof, Asher;Kaye, Paul M.
树突状细胞（DC）在启动和指导t细胞反应中发挥重要作用，部分通过产生白细胞介素-12p70 （IL-12p70）、IL-23和IL-27。然而，对DC亚群细胞因子生产能力的比较研究很少。在这里，我们比较了利什曼原虫感染后5小时至28天分离的脾CD8 α(+)、CD4（+）和双阴性（DN） DC，比较了(i) IL-12p70的产生，（ii） IL-12/23p40、IL-12p35、IL-23p19和IL-27p28 mrna的积累，以及（iii）它们指导CD4(+) t细胞分化的能力。在5 h时，常规DC （cDC）以感染剂量依赖的方式积累IL-12/23p40 （CD8 α > CD4 > DN）、IL-23p19 （CD4 > CD8 α > DN）和IL-27p28 (CD8 α > CD4 > DN) mRNA。il - 12p70仅限于CD8a+ cDC，反映了IL-12p35 mRNA的亚群特异性积累。相比之下，感染14至28天的小鼠的cDC积累了少量IL-12p40和IL-12p19的mRNA，尽管IL-27p28 mRNA仍可检测到（CD8 α > DN > CD4）。CD8 α (+) cDC分泌il - 12p70缺失，反映IL-12/23p40缺失，而非IL-12p35 mRNA积累不足。感染后早期分离的CD8 α (+) cDC指导Th1细胞分化的能力是通过IL-12/23p40介导的，而CD4+和DN cDC的这种能力不依赖于IL-12/23p40，也不是由Delta 4 notch样配体的过表达引起的。然而，DN cDC产生γ干扰素（ifn - γ），也含有罕见的CD11c(hi) DX5(+) ifn - γ产生细胞群。我们的数据说明了感染期间脾cDC亚群的广泛多样性和时间调节，并建议在解释未分离或最低纯化DC获得的数据时要谨慎。
Dendritic cells (DC) play an essential role in initiating and directing T-cell responses, in part by production of interleukin-12p70 (IL-12p70), IL-23, and IL-27. However, comparative studies on the capacity for cytokine production of DC subsets are rare. Here, we compare splenic CD8 alpha(+), CD4(+), and double-negative (DN) DC, isolated 5 h to 28 days after Leishmania donovani infection, for (i) production of IL-12p70, (ii) accumulation of IL-12/23p40, IL-12p35, IL-23p19, and IL-27p28 mRNAs, and (iii) their capacity to direct CD4(+) T-cell differentiation. At 5 h, conventional DC (cDC) accumulated mRNA for IL-12/23p40 (CD8 alpha > CD4 > DN), IL-23p19 (CD4 > CD8 alpha > DN), and IL-27p28 (CD8 alpha > CD4 > DN), in an infection dose-dependent manner. IL-12p7O was restricted to CD8a+ cDC, reflecting the subset-specific accumulation of IL-12p35 mRNA. In contrast, cDC from mice infected for 14 to 28 days accumulated little mRNA for IL-12p40 and IL-12p19, though IL-27p28 mRNA remained detectable (CD8 alpha > DN > CD4). IL-12p7O secretion by CD8 alpha(+) cDC was also absent, reflecting deficient IL-12/23p40, rather than IL-12p35, mRNA accumulation. The capacity of CD8 alpha(+) cDC isolated early after infection to direct Th1 cell differentiation was mediated through IL-12/23p40, whereas this ability in CD4+ and DN cDC was independent of IL-12/23p40 and did not result from overexpression of Delta 4 Notch-like ligand. However, DN cDC produced gamma interferon (IFN-gamma) and also contained a rare population of CD11c(hi) DX5(+) IFN-gamma-producing cells. Our data illustrate the extensive diversity in, and temporal regulation of, splenic cDC subsets during infection and suggest caution in interpreting data obtained with unfractionated or minimally purified DC.