Chemokines have crucial roles in organ development and orchestration of leukocyte migration. The chemokine CCL22 is expressed constitutively at high levels in the lymph node, but the functional significance of this expression is so far unknown. Studying a newly established CCL22-deficient mouse, we demonstrate that CCL22 expression by dendritic cells (DCs) promotes the formation of cell–cell contacts and interaction with regulatory T cells (T reg) through their CCR4 receptor. Vaccination of CCL22-deficient mice led to excessive T cell responses that were also observed when wild-type mice were vaccinated using CCL22-deficient DCs. Tumor-bearing mice with CCL22 deficiency showed prolonged survival upon vaccination, and further, CCL22-deficient mice had increased susceptibility to inflammatory disease. In conclusion, we identify the CCL22–CCR4 axis as an immune checkpoint that is crucial for the control of T cell immunity.

Objectives The NLRP3/ASC inflammasome drives host defence and autoinflammatory disorders by activating caspase-1 to trigger the secretion of mature interleukin (IL)-1β/IL-18, but its potential role in autoimmunity is speculative. Methods We generated and phenotyped Nlrp3-deficient, Asc-deficient, Il-1r-deficient and Il-18-deficient C57BL/6-lpr/lpr mice, the latter being a mild model of spontaneous lupus-like autoimmunity. Results While lack of IL-1R or IL-18 did not affect the C57BL/6-lpr/lpr phenotype, lack of NLRP3 or ASC triggered massive lymphoproliferation, lung T cell infiltrates and severe proliferative lupus nephritis within 6 months, which were all absent in age-matched C57BL/6-lpr/lpr controls. Lack of NLRP3 or ASC increased dendritic cell and macrophage activation, the expression of numerous proinflammatory mediators, lymphocyte necrosis and the expansion of most T cell and B cell subsets. In contrast, plasma cells and autoantibody production were hardly affected. This unexpected immunosuppressive effect of NLRP3 and ASC may relate to their known role in SMAD2/3 phosphorylation during tumour growth factor (TGF)-β receptor signalling, for example, Nlrp3-deficiency and Asc-deficiency significantly suppressed the expression of numerous TGF-β target genes in C57BL/6-lpr/lpr mice and partially recapitulated the known autoimmune phenotype of Tgf-β1-deficient mice. Conclusions These data identify a novel non-canonical immunoregulatory function of NLRP3 and ASC in autoimmunity.

The purpose of this study was to assess which visual function measures are most strongly associated with vision-related quality of life (VRQoL) in age-related macular degeneration (AMD). A cross-sectional study of subjects with early AMD (n = 10), intermediate AMD (n = 42) and late AMD (n = 38) was conducted. Subjects were interviewed with the Impact of Vision Impairment (IVI) questionnaire. Functional tests performed included best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA), visual acuity measured with the Moorfields Acuity Charts (MAC), contrast sensitivity, reading speed, mesopic and dark-adapted microperimetry. The relationship between VRQoL and visual function was assessed with multiple regressions controlling for confounders. Rasch analysis demonstrated the validity of the IVI to assess VRQoL through three subscales: reading and accessing information, mobility and independence, and emotional well-being. Subjects with late AMD had significant lower IVI scores on all subscales compared with intermediate and early AMD (p < 0.011). In the overall cohort, IVI subscales were associated with BCVA, LLVA, MAC-VA and contrast sensitivity (all p < 0.001). Among the subgroup of early and intermediate AMD subjects, reading and mobility subscales were significantly associated with MAC-VA (p < 0.013). These results suggest that MAC-VA is a useful, patient-relevant measure of visual impairment in AMD.

With the advent of smartphone-based fundus imaging (SBFI), a low-cost alternative to conventional digital fundus photography has become available. SBFI allows for a mobile fundus examination, is applicable both with and without pupil dilation, comes with built-in connectivity and post-processing capabilities, and is relatively easy to master. Furthermore, it is delegable to paramedical staff/technicians and, hence, suitable for telemedicine. Against this background a variety of SBFI applications have become available including screening for diabetic retinopathy, glaucoma, and retinopathy of prematurity and its applications in emergency medicine and pediatrics. In addition, SBFI is convenient for teaching purposes and might serve as a surrogate for direct ophthalmoscopy. First wide-field montage techniques are available and the combination of SBFI with machine learning algorithms for image analyses is promising. In conclusion, SBFI has the potential to make fundus examinations and screenings for patients particularly in low- and middle-income settings more accessible and, therefore, aid tackling the burden of diabetic retinopathy, glaucoma, and retinopathy of prematurity screening. However, image quality for SBFI varies substantially and a reference standard for grading appears prudent. In addition, there is a strong need for comparison of different SBFI approaches in terms of applicability to disease screening and cost-effectiveness.