Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation

SR Beaty, CE Rose, SJ Sung - The Journal of Immunology, 2007 - journals.aai.org
SR Beaty, CE Rose, SJ Sung
The Journal of Immunology, 2007journals.aai.org
Lung CD11c high dendritic cells (DC) are comprised of two major phenotypically distinct
populations, the CD11b high DC and the integrin α E β 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 …
Abstract
Lung CD11c high dendritic cells (DC) are comprised of two major phenotypically distinct populations, the CD11b high DC and the integrin α E β 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 LPS 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/monocyte-derived 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.
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