Comparative analysis of circulating dendritic cell subsets in patients with atopic diseases and sarcoidosis

Abstract

BackgroundDendritic cells (DCs) are professional antigen-presenting cells that play a crucial role in the initiation and modulation of immune responses. Human circulating blood DCs are divided into two major subsets: myeloid DCs (mDCs); and plasmacytoid DCs (pDCs). Furthermore, mDCs are subdivided into two subsets: Th1-promoting mDCs (mDC1s); and Th2-promoting mDCs (mDC2s). Although CD1a, CD1c, and CD141 are generally used for classifying mDC subsets, their adequacy as a specific marker remains unclear. We performed this study to compare circulating mDC, pDC, mDC1, and mDC2 subsets between Th1- and Th2-mediated diseases using CD1a and CD141, and to analyze the adequacy of CD1a and CD141 as a marker for mDC1s and mDC2s, respectively.MethodsThirty patients with sarcoidosis, 23 patients with atopic diseases, such as atopic bronchial asthma, and 23 healthy subjects as controls were enrolled in this study. Peripheral blood DC subsets were analyzed with flow cytometry according to expressions of CD11c, CD123, CD1a, and CD141. For functional analysis, we measured interleukin (IL) 12p40 levels produced by the sorted mDC subsets.ResultsThe sarcoidosis group showed decreased total DC (P < 0.05) and mDC counts (P < 0.05) compared to controls. The atopy group showed decreased CD1a+mDC count (P < 0.05), and increased CD1a-mDC count (P < 0.05) compared to controls. CD141+mDC count in the atopy group was higher than controls (P < 0.05). Sorted CD1a+mDCs produced higher levels of IL-12p40 than CD1a-mDCs (P = 0.025) and CD141+mDCs (P = 0.018).ConclusionsWe conclude that decreased count of CD1a+mDC and increased count of CD141+mDC may reflect the Th2-skewed immunity in atopic diseases. The results of IL-12 levels produced by the sorted mDC subsets suggested the adequacy of CD1a and CD141 as a marker for mDC1 and mDC2, respectively, in vivo.

Human CD141+ Dendritic Cells Induce CD4+ T Cells To Produce Type 2 Cytokines

“…Indeed, the addition of OX40L neutralizing antibodies to DC-T cell co-cultures substantially reduced the ability of CD141 + DCs to induce IL-13-secreting CD4 + T cells. Interestingly, CD141 + circulating DCs were found at significantly higher frequencies in subjects with house-dust mite allergy and asthma, compared with control subjects (44, 45). Moreover, CD141 expression in blood leukocytes was higher in children with acute asthma than at convalescence 6 weeks later (44).…”

Evidence of regulatory myeloid dendritic cells and circulating inflammatory epidermal dendritic cells‐like modulated by Toll‐like receptors 2 and 7/8 in adults with atopic dermatitis

“…Dendritic cells (DC) are the main antigen presenting cells (APC) and exert a relevant role of linkage between the innate and adaptive immune responses . Recent studies suggest that DC also participate in the induction of central and peripheral immunological tolerance, regulate T cell immune responses, and function as sentinels in innate immunity against microbes …”

“…Human blood DC comprise around 1–2% of peripheral blood mononuclear cells (PBMC) . They are classically defined as APC that lack other markers of leukocyte lineages (CD3, 14, 16, 19, 20, and 56) and express high levels of MHC class II (HLA‐DR) molecules .…”

“…Human blood DC comprise around 1–2% of peripheral blood mononuclear cells (PBMC) . They are classically defined as APC that lack other markers of leukocyte lineages (CD3, 14, 16, 19, 20, and 56) and express high levels of MHC class II (HLA‐DR) molecules . A DC lineage‐specific marker has not yet been identified, and the subsets of DC in humans and mice are therefore currently defined by lineage − MHC II + cells, in combination with various cell surface markers.…”

Circulating Dendritic Cells, Farm Exposure and Asthma at Early Age

“…Another study showed that cowshed dust extract reduced the allergy-inducing capacity of bone marrow DCs of mice [18]. Allergies and asthma have been shown to be associated with the numbers of DCs in adults [19][20][21][22] and in children [23][24][25], but the effect of farm exposure on circulating DCs in epidemiological settings is mainly unexplored.…”