Transcriptional profiling reveals functional dichotomy between human slan+ non-classical monocytes and myeloid dendritic cells

Human 6-sulfo LacNac-positive (slan+) cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (DC) subset. However, evidence has emerged that they may be more related to monocytes than to DCs. To gain deeper insight into the functional specialization of slan+ cells, we have compared them with both conventional myeloid DC subsets (CD1c+ and CD141+) in human peripheral blood (PB). With the use of genome-wide transcriptional profiling, as well as functional tests, we clearly show that slan+ cells form a distinct, non-DC-like population. They cluster away from both DC subsets, and their geneexpression profile evidently suggests involvement in distinct inflammatory processes. An extensive transcriptional meta-analysis confirmed the relationship of slan+ cells with the monocytic compartment rather than with DCs. From a functional perspective, their ability to prime CD4+ and CD8+ T cells is relatively low. Combined with the finding that “antigen presentation by MHC class II” is at the top of under-represented pathways in slan+ cells, this points to a minimal role in directing adaptive T cell immunity. Rather, the higher expression levels of complement receptors on their cell surface, together with their high secretion of IL-1b and IL-6, imply a specific role in innate inflammatory processes, which is consistent with their recent identification as non-classical monocytes. This study extends our knowledge on DC/monocyte subset biology under steady-state conditions and contributes to our understanding of their role in immune-mediated diseases and their potential use in immunotherapeutic strategies

Human bone marrow-derived myeloid dendritic cells show an immature transcriptional and functional profile compared to their peripheral blood counterparts and separate from slan+ non-classical monocytes

The human bone marrow (BM) gives rise to all distinct blood cell lineages, including CD1c+ (cDC2) and CD141+ (cDC1) myeloid dendritic cells (DC) and monocytes. These cell subsets are also present in peripheral blood (PB) and lymphoid tissues. However, the difference between the BM and PB compartment in terms of differentiation state and immunological role of DC is not yet known. The BM may represent both a site for development as well as a possible effector site and so far, little is known in this light with respect to different DC subsets. Using genome-wide transcriptional profiling we found clear differences between the BM and PB compartment and a location-dependent clustering for cDC2 and cDC1 was demonstrated. DC subsets from BM clustered together and separate from the corresponding subsets from PB, which similarly formed a cluster. In BM, a common proliferating and immature differentiating state was observed for the two DC subsets, whereas DC from the PB showed a more immune-activated mature profile. In contrast, BM-derived slan+ non-classical monocytes were closely related to their PB counterparts and not to DC subsets, implying a homogenous prolife irrespective of anatomical localization. Additional functional tests confirmed these transcriptional findings. DC-like functions were prominently exhibited by PB DC. They surpassed BM DC in maturation capacity, cytokine production, and induction of CD4+ and CD8+ T cell proliferation. This first study on myeloid DC in healthy human BM offers new information on steady state DC biology and could potentially serve as a starting point for further research on these immune cells in healthy conditions as well as in diseases

The incidence of rhegmatogenous retinal detachment in the Netherlands: Dutch Rhegmatogenous Retinal Detachment Study Group

Objective: To estimate the incidence and characteristics of rhegmatogenous retinal detachment (RRD) in The Netherlands in 2009. Design: Retrospective, observational case series. Participants: All patients with RRD in the Dutch population in 2009. Methods: By reviewing surgical logs, cases of primary RRD repair in 2009 were identified. Exclusion criteria included RRD before 2009 and exudative, tractional, or traumatic retinal detachments. Patient demographics, date of surgery, and lens status were documented. Incidence of RRD and 95% confidence intervals (CIs) were calculated based on the Poisson distribution. Age distribution, male-to-female ratio, and proportion of RRD patients with prior cataract extraction (CE) were determined. A Student t test was used to examine differences in the incidence of RRD between groups. Main Outcome Measures: Annual RRD incidence in the population and per gender-adjusted age category and proportion of RRD patients with prior CE. Results: The annual RRD incidence was 18.2 per 100 000 people (95% CI, 11.4–18.8), with a peak incidence of 52.5 per 100 000 people (95% CI, 29.4–56.8) between 55 and 59 years of age. The Bilateral RRD rate was 1.67%. Macula-off presentation occurred in 54.5% of all RRD patients. Prior CE was noted in 33.5% of RRD eyes. The male-to-female ratio was 1.3:1, and RRD incidence was statistically significantly more frequent in males (P 0.0001). Conclusions: Rhegmatogenous retinal detachment is predominantly a disease of the population older than 50 years, and males are more susceptible to RRD. The annual RRD incidence is highly dependent on demographic characteristics