Compartmental Imbalance and Aberrant Immune Function of Blood CD123+ (Plasmacytoid) and CD11c+ (Myeloid) Dendritic Cells in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a pruritic, chronically relapsing skin disease in which Th2 cells play a crucial role in cutaneous and extracutaneous immune reactions. In humans, CD11c+CD123− myeloid dendritic cells (mDC) and CD11c−CD123+ plasmacytoid DC (pDC) orchestrate the decision-making process in innate and acquired immunity. Since the number and function of these blood dendritic cell (DC) subsets reportedly reflect the host immune status, we studied the involvement of the DC subsets in the pathogenesis of AD. Patients with AD had an increased DC number and a low mDC:pDC ratio with pDC outnumbering mDC in the peripheral blood compared with normal subjects and psoriasis patients (a Th1 disease model group). The mDC:pDC ratio was correlated with the total serum IgE level, the ratio of IFN-γ-producing blood cells:IL-4-producing blood cells, and the disease severity. In vitro allogeneic stimulation of naive CD4+ cells with atopic DC showed that the ability of pDC for Th1 induction was superior or comparable to that of mDC. In skin lesions, pDC infiltration was in close association with blood vessels expressing peripheral neural addressins. Therefore, compartmental imbalance and aberrant immune function of the blood DC subsets may deviate the Th1/Th2 differentiation and thus induce protracted allergic responses in AD.

Macrophage-derived chemokine (MDC)/CCL22 produced by monocyte derived dendritic cells reflects the disease activity in patients with atopic dermatitis

“…However, the chemokine production by MoDCs in AD patients has not yet been completely elucidated. The ratio of blood MoDCs against pDCs has been recently reported to decrease in AD patients [19]. In addition, an insufficiency of IL-12 production by DCs in AD patients has also been identified [20].…”

TLR9- and FcεRI-Mediated Responses Oppose One Another in Plasmacytoid Dendritic Cells by Down-Regulating Receptor Expression

“…Moreover, these DC have recently been identified in allergic lesions in the nose (16) and are found at higher frequencies in certain allergic conditions (17). In fact, pDC are often referred to as DC2 because of the initial work linking them to the induction of Th2 responses in vitro (18).…”

Dendritic Cells in Atopic Dermatitis: Expression of FcεRI on Two Distinct Inflammation-Associated Subsets

“…If so, pDCs may transmit signals from innate to adaptive immunity. Given the potent Th1 polarization elicited by virus-activated pDCs [42], in AD these cells may contribute to the switch from a Th2-mediated acute disease to a Th1-driven chronic disease [43, 44]. …”