Innate Immune Cells to the Help

A study by Halim and Steer (2014) in this issue of Immunity shows that innate lymphoid cells type 2 (ILC2s) are crucial for inducing adaptive T helper 2 immunity by providing interleukin-13. Another study by van Dyken et al. (2014) shows that ILC2s control eosinophilia and alternative activation of macrophages

Langerhans cells : sensing the environment in health and disease

In the last few decades, our understanding of Langerhans cells (LCs) has drastically changed based on novel findings regarding the developmental origin and biological functions of these epidermis-specific resident immune cells. It has become clear that LCs not only exert pivotal roles in immune surveillance and homeostasis but also impact on pathology by either inducing tolerance or mediating inflammation. Their unique capabilities to self-renew within the epidermis, while also being able to migrate to lymph nodes in order to present antigen, place LCs in a key position to sample the local environment and decide on the appropriate cutaneous immune response. Exciting new data distinguishing LCs from Langerin(+) dermal dendritic cells (DCs) on a functional and ontogenic level reveal crucial roles for LCs in trauma and various skin pathologies, which will be thoroughly discussed here. However, despite rapid progress in the field, the exact role of LCs during immune responses has not been completely elucidated. This review focuses on what mouse models that have been developed in order to enable the study of murine LCs and other Langerin-expressing DCs have taught us about LC development and function

Lung inflammation and immunity : report from the 12th ERS Lung Science conference

The European Respiratory Society (ERS) seeks to alleviate suffering from respiratory diseases and promote lung health through research, dissemination of knowledge, and medical and public education. In support of this mission, the ERS organises the annual Lung Science Conference (LSC). This world-class research meeting brings together leading experts on topics that are of relevance to respiratory medicine. Furthermore, at the LSC, one of the main focuses is early-career physicians and scientists who are involved in respiratory research, as these are the future leaders of the field [1]. Inflammatory diseases of the lung are a major cause of morbidity and mortality. In March 2014, international experts met for the 12th LSC in Estoril, Portugal, to present and discuss novel findings in the field of “Lung Inflammation and Immunity”, recognising that inflammation is the main pathogenic process in many respiratory diseases, such as asthma and infection, and a significant contributor to many others [2, 3]. Old and recent anti-inflammatory and/or immunomodulating drugs are the main tools of our current treatment in many respiratory diseases, and new drugs targeting inflammatory pathways are being developed. This was discussed in an early evening session “The new drug discovery paradigm” by Tomas Mustelin (Respiratory, Inflammatory, and Autoimmune Diseases, MedImmune, Gaithersburg, MD, USA) and Robert Strieter (Novartis Institutes for BioMedical Research, Cambridge, MA, USA), who were both involved in academic respiratory research before joining pharmaceutical companies. Part of the 2014 LSC was focused on the mechanisms of allergy and asthma, but other fields of interest were discussed, particularly lung fibrosis, chronic obstructive pulmonary disease and emphysema, pulmonary hypertension, and lung transplantation

How a farming environment protects from atopy

It is now well established that the exposure to certain environments such as farms has the potential to protect from the development of allergies later in life. This protection is achieved when repeated exposure to the farming environment occurs early in life, but persists when children spend sufficient amount of time in contact with livestock and hay, and drink unpasteurized milk. The capacity of farm dust to protect from allergy development lies, amongst others, in the microbe composition in the farm. These protective microbes release various metabolites and cell wall components that change farmers' home dust composition, when compared to urbanized home dust. Additionally, they can colonize various barrier sites (skin, lung, intestine) in farmers' children, leading to persistent changes in the way their immune system and their barrier cells respond to environmental allergens

Professional and 'amateur' antigen-presenting cells in type 2 immunity

Dendritic cells (DCs) are critical for the activation of naive CD4(+) T cells and are considered professional antigen-presenting cells (APCs), as are macrophages and B cells. Recently, several innate type 2 immune cells, such as basophils, mast cells (MCs), eosinophils, and innate type 2 lymphocytes (ILC2), have also emerged as harboring APC behavior. Through surface expression or transfer of peptide-loaded MHCII, expression of costimulatory and co-inhibitory molecules, as well as the secretion of polarizing cytokines, these innate cells can extensively communicate with effector and regulatory CD4(+) T cells. An exciting new concept is that the complementary tasks of these 'amateur' APCs contribute to shaping and regulating adaptive immunity to allergens and helminths, often in collaboration with professional APCs

The hygiene hypothesis : immunological mechanisms of airway tolerance

The hygiene hypothesis was initially proposed as an explanation for the alarming rise in allergy prevalence in the last century. The immunological idea behind this hypothesis was a lack of infections associated with a Western lifestyle and a consequential reduction in type 1 immune responses. It is now understood that the development of tolerance to allergens depends on microbial colonization and immunostimulatory environmental signals during early-life or passed on by the mother. These environmental cues are sensed and integrated by barrier epithelial cells of the lungs and possibly skin, which in turn instruct dendritic cells to regulate or impede adaptive T cell responses. Recent reports also implicate immunoregulatory macrophages as powerful suppressors of allergy by the microbiome. We propose that loss of adequate microbial stimulation due to a Western lifestyle may result in hypersensitive barrier tissues and the observed rise in type 2 allergic disease

Cellular networks controlling Th2 polarization in allergy and immunity

In contrast to the development of Th1 (type 1 T helper cells), Th17 and Treg (regulatory T cells), little is known of the mechanisms governing Th2 development, which is important for immunity to helminths and for us to understand the pathogenesis of allergy. A picture is emerging in which mucosal epithelial cells instruct dendritic cells to promote Th2 responses in the absence of IL-12 (interleukin 12) production and provide instruction through thymic stromal lymphopoieitin (TSLP) or granulocyte-macrophage colony stimulating factor (GM-CSF). At the same time, allergens, helminths and chemical adjuvants elicit the response of innate immune cells like basophils, which provide more polarizing cytokines and IL-4 and reinforce Th2 immunity. This unique communication between cells will only be fully appreciated if we study Th2 immunity in vivo and in a tissue-specific context, and can only be fully understood if we compare several models of Th2 immune response induction

SysML Model-Driven Approach to Verify Blocks Compatibility

International audienceIn the component paradigm, the system is seen as an assembly of heterogeneous components, where the system reliability depends on these components compatibility. In our approach, we focus on verifying compatibility of components modelled with SysML diagrams. Thus, we model component interactions with sequence diagrams (SDs) and components with SysML blocks. The SDs constitute a good start point for compatibility verification. However, this verification is still inapplicable directly on SDs, because they are expressed in informal language. Thus, to apply a verification method, it is necessary to translate the SDs into formal models, and then verify the wanted properties. In this paper, we propose a high-level model-driven approach which consists of an ATL grammar that automates the transformation of SDs into interface automata. Also, to allow an easy use of Ptolemy tool to verify properties on automata, we have proposed some Acceleo templates, which generate the Ptolemy entry specification

Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming

Foxp3(+) regulatory T cells (Tregs) maintain immune homoeostasis through mechanisms that remain incompletely defined. Here by two-photon (2P) imaging, we examine the cellular dynamics of endogenous Tregs. Tregs are identified as two non-overlapping populations in the T-zone and follicular regions of the lymph node (LN). In the T-zone, Tregs migrate more rapidly than conventional T cells (Tconv), extend longer processes and interact with resident dendritic cells (DC) and Tconv. Tregs intercept immigrant DCs and interact with antigen-induced DC: Tconv clusters, while continuing to form contacts with activated Tconv. During antigen-specific responses, blocking CTLA4-B7 interactions reduces Treg-Tconv interaction times, increases the volume of DC: Tconv clusters and enhances subsequent Tconv proliferation in vivo. Our results demonstrate a role for altered cellular choreography of Tregs through CTLA4-based interactions to limit T-cell priming