Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation
Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation
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DOI：
10.4049/jimmunol.178.3.1882
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Sung, Sun-Sang J.
中科院分区：
文献类型：
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作者：
Beaty, Steven R.;Rose, C. Edward, Jr.;Sung, Sun-Sang J.
肺CD11c（高）树突状细胞（DC）由两个主要的表型不同的群体组成，即CD11b（高）DC和整合素α(E)β(+)(7) DC（CD103(+) DC）。为了检验它们在功能上是否可区分，进行了全基因芯片研究和实时PCR分析。发现两种主要的CD11c（高）DC类型在趋化因子mRNA表达上存在显著差异。CD11b（高）DC是一种主要的分泌细胞类型，在稳态下至少高度表达16种趋化因子mRNA，而CD103(+) DC仅高度表达6种。对包括巨噬细胞在内的肺CD11c（高）细胞进行细胞内趋化因子染色，以及对分选纯化的CD11c（高）细胞培养上清液进行ELISA测定，进一步表明CD11b（高）DC分别产生所研究的14种趋化因子中的9种和7种中的5种的最高水平。在体外和体内LIPS刺激后，CD11b（高）DC仍然是10种产量最高的趋化因子中的7种的最高产生者。气道高反应性和肺部炎症的诱导使肺CD11b（高）DC数量显著增加，并且与巨噬细胞相比，它们产生的12种主要趋化因子中的11种数量相当或更高。尽管不是主要产生者，但CD103(+) DC在稳态和炎症状态下都产生最高量的Th2刺激趋化因子CCL17/胸腺和活化相关趋化因子以及CCL22/单核细胞衍生趋化因子。值得注意的是，CCL22/单核细胞衍生趋化因子对CD4(+) T细胞增殖表现出调节作用。进一步的功能分析表明，两种DC类型诱导的Th亚群发育相当。这些研究表明，肺CD11b（高）DC是趋化因子产生中最重要的白细胞类型之一，并且在这种分泌功能上很容易与CD103(+) DC区分开来。
Lung CD11c(high) dendritic cells (DC) are comprised of two major phenotypically distinct populations, the CD11b(high) DC and the integrin alpha(E)beta(+)(7) DC (CD103(+) DC). To examine whether they are functionally distinguishable, global microarray studies and real-time PCR analysis were performed. Significant differences between the two major CD11c(high) DC types in chemokine mRNA expression were found. CD11b(high) DC is a major secretory cell type and highly expressed at least 16 chemokine mRNA in the homeostatic state, whereas CD103(+) DC highly expressed only 6. Intracellular chemokine staining of CD11c(high) lung cells including macrophages, and ELISA determination of sort-purified CD11c(high) cell culture supernatants, further showed that CD11b(high) DC produced the highest levels of 9 of 14 and 5 of 7 chemokines studied, respectively. Upon LIPS stimulation in vitro and in vivo, CD11b(high) DC remained the highest producer of 7 of 10 of the most highly produced chemokines. Induction of airway hyperreactivity and lung inflammation increased lung CD11b(high) DC numbers markedly, and they produced comparable or higher amounts of 11 of 12 major chemokines when compared with macrophages. Although not a major producer, CD103+ DC produced the highest amounts of the Th2-stimulating chemokines CCL17/thymus and activation-related chemokine and CCL22/monocytederived chemokine in both homeostasis and inflammation. Significantly, CCL22/monocyte-derived chemokine exhibited regulatory effects on CD4(+) T cell proliferation. Further functional analysis showed that both DC types induced comparable Th subset development. These studies showed that lung CD11b(high) DC is one of the most important leukocyte types in chemokine production and it is readily distinguishable from CD103(+) DC in this secretory function.