In the skin, the lack of markers permitting the unambiguous identification of macrophages and of conventional and monocyte-derived dendritic cells (DCs) complicates understanding of their contribution to skin integrity and to immune responses. By combining CD64 and CCR2 staining, we successfully identified each of these cell types and studied their origin, transcriptomic signatures, and migratory and T cell stimulatory properties. We also analyzed the impact of microbiota on their development and their contribution to skin inflammation during contact hypersensitivity. Dermal macrophages had a unique scavenging role and were unable to migrate and activate T cells. Conventional dermal DCs excelled both at migrating and activating T cells. In the steady-state dermis, monocyte-derived DCs are continuously generated by extravasated Ly-6C(hi) monocytes. Their T cell stimulatory capacity combined with their poor migratory ability made them particularly suited to activate skin-tropic T cells. Therefore, a high degree of functional specialization occurs among the mononuclear phagocytes of the skin.

Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1+ DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1+ human DC. Assessment of the immunoactivation potential of XCR1+ human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1+ and XCR1− human DC in CD34+ progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1− CD34-DC are similar to canonical MoDC, whereas XCR1+ CD34-DC resemble XCR1+ blood DC (bDC). XCR1+ DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1+ DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1+ CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1+ bDC. Hence, it is feasible to generate high numbers of bona fide XCR1+ human DC in vitro as a model to decipher the functions of XCR1+ bDC and as a potential source of XCR1+ DC for clinical use.

Alexandre et al. demonstrate the XCR1+ DCs are instrumental in memory CD8+ T cell responses to Listeria, VSV or vaccinia virus infection, but not CMV. Depending on the infection, robust memory CTL responses require cytokine- and chemokine-dependent cross-talk between XCR1+ DCs and NK cells or other IFN-γ–producing lymphocytes.

Deadwood is one of the four elements taken into account in this review of indicators and field methods and is often considered as a key indicator of forest biodiversity. We have analysed the main types of surveys and have realised how greatly the needs and constraints used to monitor deadwood can vary among them. For instance, classical National Forest Inventories usually tend to avoid time-consuming collecting methods. In the wide variety of existing definitions of deadwood, such inventories require simple and clear definitions, especially in terms of quantified thresholds. Thus, deadwood is properly described by characterising several components, such as snags, logs, stumps, branches and fine woody debris. Deadwood sampling methods alter depending on the different components and dimensions considered (standing dead trees, lying dead trees and branches, etc. assessed quantitatively). Attributes such as tree species and stage of decay are used mainly to qualify the deadwood components. The deadwood volume estimations are usually based on classical approaches already applied to living or felled trees: volume equations and/or formulas giving the volumes of common geometric solids. The purpose of this paper is to focus on different deadwood assessment techniques and to provide the information necessary to identify the most relevant methods for collecting deadwood data. The latter is used to build indicators that characterise the evolution of forest biodiversity at the scale of large forest territories.

Hematological malignancies treatment improved over the last years resulting in increased achievement of complete or partial remission, but unfortunately high relapse rates are still observed. Therefore, sustainment of long-term remission is crucial. Immune system has a key role in tumor surveillance. Natural killer (NK) cells, at the frontier of innate and adaptive immune system, have a central role in tumor cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. Nevertheless, tumor cells develop various mechanisms to escape from NK cells innate immune pressure. Abnormal NK cytolytic functions have been described in nearly all hematological malignancies. We present here various mechanisms involved in the escape of hematological malignancies from NK cells surveillance: NK cells quantitative deficiency and NK cell qualitative deficiency by increased inhibition signaling or decreased activating stimuli. A challenge of immunotherapy is to restore an efficient antitumor response. A combination of classical therapy plus immune modulation strategies will soon become a standard of care for hematological malignancies.

Background: Randomized control trials performed in selected populations of severe eosinophilic asthmatics have shown that mepolizumab, an anti-IL5 therapy, was able to reduce exacerbations and OCS maintenance dose and in some studies, to improve asthma control and lung function.Objective: The aim of this study was to confirm the results of the RCTs in real-life in a population of 116 severe eosinophilic asthmatics treated with mepolizumab and who were followed up at the asthma clinic every month for at least 18 months. Severe asthmatics underwent FENO, lung function, asthma control and quality of life questionnaires, sputum induction and gave a blood sample at baseline, after 6 months and then every year. Results:We found a significant reduction in exacerbations by 85% after 6 months (P < .0001), which was maintained over time. We also found a significant and maintained reduction by 50% in the dose of oral corticosteroids (P < .001). Patients improved their ACT (+5.31pts, p<0.0001) ACQ (-1.13pts, P < .0001) and their AQLQ score (+1.24, P < .0001) at 6 months and this was maintained during follow-up. Only 37% reached asthma control (ACQ <1.5, ACT> 20). We observed a progressive increase in post-BD FEV1 that reached significance after 18 months (190ml or 11%, P < .01). Patients improving their FEV1had higher baseline sputum eosinophils than those not improving airway caliber. We found a significant reduction in sputum eosinophil counts by 60% after 6 months (P < .01) and a maintained reduction in blood eosinophil counts by 98% (P < .0001). Conclusion:In our real-life study, we confirm the results published in the RCTs showing a sharp reduction in exacerbation and oral corticosteroids dose and an improvement in asthma control and quality of life. Clinical relevance: Mepolizumab is efficient in severe eosinophilic asthma in real life. K E Y W O R D S eosinophils, exacerbations, lung function, mepolizumab, severe asthma, sputum

Summary Recent advances in chronic lymphocytic leukaemia (CLL) treatment, more particularly through upfront use of anti‐CD20 monoclonal antibodies, have prolonged patient progression‐free survival. Nonetheless, apart from allogeneic stem cell transplantation, no curative treatment is available. One possible explanation for the lack of cure in CLL could be a defective immune anti‐tumour response. As the result of abnormal HLA class I molecule expression, CLL cells escape from specific T‐lymphocyte immunity but should be the target for the innate natural killer (NK) cell‐mediated immune response. Defective NK cytotoxicity as the result of decreased expression of the natural cytotoxicity receptors (NCRs) NKp30/NCR3, NKp44/NCR2 and NKp46/NCR1 has been described in haematological malignancies such as acute myeloid leukaemia. This prompted us to focus our attention on NCR expression on NK cells from patients with CLL. Although we failed to detect any difference between CLL patients and healthy age‐matched controls, a precise analysis of clinical data showed a correlation between decreased NCR expression and poor prognosis factors such as low haemoglobin level, high (> 30 × 109 per litre) lymphocyte count or elevated C‐reactive protein. Together, these observations support the rationale for restoration of normal NK cell functions in patients with CLL, putatively through the use of immune therapy protocols that already have demonstrated some benefit in acute myeloid leukaemia such as interleukin‐2 plus histamine dihydrochloride.

In mice, CD8α+ myeloid dendritic cells (mDC) optimally cross-present Ags to CD8+ T cells and respond strongly to TLR3 ligands. Although equivalent DC have been identified by comparative genomic analysis and functional studies in humans as XCR1+CD141 (BDCA-3)+Clec9A+cell adhesion molecule 1+ mDC, and in sheep as CD26+ mDC, these cells remained elusive in nonhuman primates. To remedy this situation, we delineated precisely DC and monocyte populations by 12-color flow cytometry and transcriptomic analyses in healthy rhesus macaques. We identified a new mDC population, with strong phenotypic and transcriptional homology to human CD141+ and murine CD8α+ mDC, including XCR1 membrane expression as a conserved specific marker. In contrast, high CD11c expression was not characteristic of mDC in macaques, but of CD16+ monocytes. Like their human and murine homologs, simian XCR1+ mDC had much stronger responses to TLR3 stimulation than other myeloid cells. The importance of this new mDC population was tested in SIVmac251 infection, the most relevant animal model for pathogenic HIV-1 infection and vaccination. This population increased sharply and transiently during acute infection, but was reduced in blood and spleen during advanced disease. The identification of XCR1+ mDC in rhesus macaques opens new avenues for future preclinical vaccinal studies and highlights XCR1 as a prime candidate for targeted vaccine delivery.