The high-affinity IgE receptor FcεRI is constitutively expressed in mast cells and basophils and is required for transmitting stimulatory signals upon engagement of IgE-bound allergens. FcεRI is also constitutively expressed in dendritic cells (DCs) and monocytes in humans; however, the specific functions of the FcεRI expressed by these cells are not completely understood. Here, we found that FcεRI expressed by human blood DC antigen 1-positive (BDCA1 + ) DCs and monocytes, but not basophils, traffics to endolysosomal compartments under steady-state conditions. Furthermore, IgE bound to FcεRI on BDCA1 + DCs was rapidly endocytosed, transported to the lysosomes, and degraded in vitro. IgE injected into mice expressing human FcεRIα (FCER1A-Tg mice) was endocytosed by conventional DCs and monocytes, and endocytosis was associated with rapid clearance of circulating IgE from these mice. Importantly, this rapid IgE clearance was dependent on monocytes or DCs but not basophils. These findings strongly suggest that constitutive internalization of human FcεRI by DCs and monocytes distinctively contributes to serum IgE clearance.

The use of proteins as monomers for materials assembly enables customization of chemical, physical, and functional properties. However, natural materials-forming proteins are difficult to produce as recombinant protein monomers and require harsh conditions to initiate assembly. We have generated materials using the recombinant transcription factor Ultrabithorax, a Drosophila melanogaster protein not known or anticipated to form extended oligomers in vivo. Ultrabithorax self-assembles at the air-water interface into nanoscale fibers, which further associate to form macroscale films, sheets, ropes, and tethered encapsulates. These materials self-adhere, allowing construction of more complex architectures. The Ultrabithorax sequence contains two regions capable of generating materials, only one of which contains motifs found in elastomeric proteins. However, both minimal regions must be included to produce robust materials. Relative to other protein-based materials, Ultrabithorax assembles at significantly reduced concentrations, on faster timescales, and under gentler conditions, properties that facilitate future materials engineering and functionalization.

The maintenance of immune tolerance requires the deletion of self-reactive T cells in the thymus. The expression of tissue-specific antigen genes (TSAs) by thymic epithelial cells is critical for this process and depends on the activity of the Autoimmune Regulator (Aire) protein, however, the molecular mechanism(s) Aire uses to target TSA gene loci are unknown. Here we identified two Aire-interacting proteins – activating transcription factor 7 interacting protein (ATF7ip) and methyl CpG binding protein 1 (MBD1) –that are required for Aire’s targeting of TSA geneloci. Moreover, Mbd1−/− mice developed pathological autoimmunity and had a defect in Aire-dependent thymic TSA gene expression underscoring the critical importance of Aire’s interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance.

Early studies regarding the function of FcεRI in dendritic cells (DCs) and monocytes have focused on its role in mediating inflammatory signaling and enhancing T cell immunity. It has been the case in part because FcεRI is the major receptor that mediates allergic inflammatory signaling in mast cells and basophils and because DCs and monocytes are antigen presenting cells capable of activating naϊve and/or effector T cells. These studies have led to the general belief that FcεRI-mediated DC signaling and antigen presentation promote development and activation of Th2 cells and contribute to allergic inflammatory diseases. However, this belief has long suffered from a lack of evidence. Recently, studies have emerged that provide evidence supporting an opposing role: that FcεRI on DCs instead promotes immune homeostasis and regulation. In this review, we will update the current status of our understanding of FcεRI biology and function, with a specific focus on DCs and monocytes.

Dendritic cells (DCs) significantly contribute to the pathology of several mouse lung disease models. However, little is known of the contribution of DCs to human lung diseases. In this study, we examined infiltration with BDCA1+ DCs of human lungs in patients with interstitial lung diseases or asthma. Using flow cytometry, we found that these DCs increased by 5∼6 fold in the lungs of patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are both characterized by extensive fibrosis in parenchyma. The same DC subset also significantly increased in the lung parenchyma of patients with chronic obstructive pulmonary disease, although the degree of increase was relatively modest. By employing immunofluorescence microscopy using FcεRI and MHCII as the specific markers for BDCA1+ DCs, we found that the numbers of BDCA1+ DCs also significantly increased in the airway epithelium of Th2 inflammation-associated asthma. These findings suggest a potential contribution of BDCA1+ DCs in human lung diseases associated with interstitial fibrosis or Th2 airway inflammation.