Human blood DCs encompass pDCs and two subsets of mDCs: CD1c(+) mDCs and CD141(+) mDCs. The rare CD141(+) DC population is thought to be the equivalent of mouse CD8α(+) cDCs that play a significant role in antigen cross-presentation. Here, we analyzed by Q-PCR TLR1-10 expression in blood DC subsets. Whereas CD1c(+) DCs express all TLR except TLR9, CD141(+) DCs present a more restricted pattern with high expression of TLR3 and -10, expression of TLR1,-2, -6, and -8, and lack of TLR4, -5, -7, and -9. The in vitro analysis of isolated mDC subset reponsiveness to an extensive panel of TLR ligands confirmed these results, with CD141(+) DCs responding only to TLR1/2, -3, and -7/8. The cytokine/chemokine production profile of isolated CD141(+) DCs was also more restricted, as they produced mainly proinflammatory cytokines but no IL-12 and to a lower level, in comparison with CD1c(+) DCs, except for CXCL10, CCL5, and IFN-β. In contrast, with the use of a whole blood assay, we found that CD141(+) DCs produce IL-12 in response to TLR1/2, -3, and more surprisingly, -9. Finally, both mDC subsets are potent inducers of Th1 response, particularly after TLR3 triggering. Taken together, these data confirmed functional differences between blood mDC subsets. The major response of CD141(+) mDCs to TLR3 ligand and their cytokine production pattern suggest a role for these cells in antiviral immunity.

IL-22 is mainly produced at barrier surfaces by T cells and innate lymphoid cells and is crucial to maintain epithelial integrity. However, dysregulated IL-22 action leads to deleterious inflammation and is involved in diseases such as psoriasis, intestinal inflammation and cancer. IL-22BP is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We show both in rats and mice that, in the steady state, the main source of IL-22BP is constituted by a subset of conventional dendritic cells (DC) in lymphoid and non lymphoid tissues. In mouse intestine, IL-22BP was specifically expressed in lamina propria CD103+CD11b+ DC. In humans, IL-22BP was expressed in immature monocyte-derived DC (MDDC) and strongly induced by retinoic acid (RA) but dramatically reduced upon maturation. Our data suggest that a subset of immature DC may actively participate in the regulation of IL-22 activity in the gut by producing high levels of IL-22BP.

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FIG 2. Basophils from allergic patients do not respond to TSLP and do not express IL-7Ra. Whole blood samples from HDs (empty bars, n 5 5) and allergic patients (black bars, n 5 8) were stimulated for 6 hours with IL-3, TSLP, anti-Fc 3RI antibody, or medium and analyzed by FCM. Gating strategy on whole blood (A). Intracellular P-STAT5 expression in basophils (left) and mDCs (right) (B). CD203c (left) and CCR3 (right) expression on basophils (C). % of IL-7Ra-and TSLPR-expressing basophils (left) or mDCs (right) (D). Data are shown as mean 6 SEM.

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Allergen-specific serum immunoglobulin E determination with the fluoroimmunoenzymatic method ImmunoCAP(®) is a highly repeatable, reproducible, and accurate method which may be considered as a single analyte assay in view of the EN ISO 15189 accreditation procedure.

We have previously reported that a distinct subset of splenic CD4À rat dendritic cells (DC) induces a rapid and caspaseindependent apoptosis-like cell death in a large number of tumor cells in vitro. NKp46+ . KDC numbers could be specifically and strongly (up to 10-fold) enhanced by Flt3L in vivo. The OSRGa cell line derived from the osteosarcoma tumor was killed and phagocytosed in vitro by both normal and Flt3L-induced splenic KDC. Such tumor antigen-loaded KDC were used to s.c. vaccinate progressive tumor-bearing rats. Vaccination with OSRGa-loaded KDC but not KDC loaded with irrelevant tumor cells (Jurkat) delayed tumor progression or even induced tumor regression. This vaccine effect was not observed in CD8 T cell-depleted animals and protective against tumor rechallenge. These results suggest that KDC possess the intrinsic capability not only to kill and then engulf tumor cells but also to efficiently cross-present tumor cellderived antigen in vivo and subsequently induce an adaptive antitumor immune response. [Cancer Res 2008;68(22):9433-40]

In this study, we aimed at evaluating the contribution of an extended myositis-related antibodies (Abs) determination by immunoblot to the diagnosis, classification, and prognosis of idiopathic inflammatory myositis (IIM). Medical records of all the patients (n = 237) with myositis-related Ab requests addressed to our department over a one-year period were retrospectively analyzed. Patients were classified as IIM, auto-immune disease (AID) other than IIM, and other diagnosis, and examined for their Ab profiles as determined by immunoblot. Ab positivity was qualified semi-quantitatively as low or strong according to the manufacturer's recommendations. Among the 45 Ab-positive patients, 49% were diagnosed an IIM, 22% another AID, and 29% another diagnosis. The clinico-serological patterns of the myositis-related Ab patients fully recapitulated those described in the literature. Among non-IIM patients, anti-PM-Scl was the most frequently detected Ab (38%), followed by anti-Mi-2 (15%), and anti-OJ (12%). Importantly, strong Ab positivity was significantly more detected in IIM vs. non-IIM patients (82% vs. 35%; p = .002). This difference was further increased when comparing MSAs only (95% vs. 36%; p = .0004). Accordingly, strong Ab positivity associated with high specificity (96%) and positive likelihood ratio (pLR =12) for IIM. Our data suggest that while myositis-related Ab, including MSA, can be detected by immunoblot in non-IIM patients, strong positivity is nevertheless highly predictive of IIM. In conclusion, this work suggests that relevant clinical contribution to IIM is provided by the immunoblot determination of myositis-related Ab, more especially when considering strong positive detection of MSA.