Summary The skin is one of the most important organs in the body, providing integrity and acting as a barrier to exclude microbes, allergens and chemicals. However, chronic skin inflammation can result when barrier function is defective and immune responses are dysregulated or misdirected against harmless or self-antigens. During the last 15 years interleukin (IL)-17 cytokines have emerged as key players in multiple inflammatory disorders, and they appear to be especially prominent in skin inflammation. IL-17 cytokines produced by T cells and other cell types potently activate keratinocytes to promote inflammation in a feed-forward loop. Given this key pathogenic role of the IL-17 pathway in autoimmune and inflammatory disease, it has been the focus of intense efforts to target therapeutically. The inflammatory effects of IL-17 can be targeted directly by blocking the cytokine or its receptor, or indirectly by blocking cytokines upstream of IL-17-producing cells. Psoriasis has been the major success story for anti-IL-17 drugs, where they have proven more effective than in other indications. Hidradenitis suppurativa (HS) is another inflammatory skin disease which, despite carrying a higher burden than psoriasis, is poorly recognized and under-diagnosed, and current treatment options are inadequate. Recently, a key role for the IL-17 pathway in the pathogenesis of HS has emerged, prompting clinical trials with a variety of IL-17 inhibitors. In this review, we discuss the roles of IL-17A, IL-17F and IL-17C in psoriasis and HS and the strategies taken to target the IL-17 pathway therapeutically.

The neurotransmitter oxytocin plays an important role in social affiliation. Low oxytocin levels and defects in the oxytocin receptor have been reported in childhood autism. However, little is known about oxytocin’s post-receptor signaling pathways in autism. Oxytocin signals via stimulatory and inhibitory G proteins. c-fos mRNA expression has been used as a marker of OT signaling as well as of G protein signaling. Herein, we hypothesized that oxytocin and its signaling pathways would be altered in children with autism. We measured plasma oxytocin levels by ELISA, G-protein and c-fos mRNA by PCR, and G proteins by immunoblot in cultured peripheral blood mononuclear cells (PBMCs) in children with autism and in age-matched controls. Males with autism displayed elevated oxytocin levels compared to controls (p<0.05). Children with autism displayed significantly higher mRNA for stimulatory G proteins compared to controls (p<0.05). Oxytocin levels correlated strongly positively with c-fos mRNA levels, but only in control participants (p<0.01). Oxytocin, G-protein, and c-fos mRNA levels correlated inversely with measures of social and emotional behaviors, but only in control participants. These data suggest that children with autism may exhibit a dysregulation in oxytocin and/or its signaling pathways.

Given the well-documented symptom overlap between Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD), careful evaluation of potential differentiation and overlap is critical for accurate diagnostic decisions. Although research has considered the use of symptom checklists and parent/teacher report questionnaires for symptom differentiation, standardized observational methods, typically utilized in the context of ASD evaluation, have received less attention. The present study examined the continuum of communication and social interaction impairment for youth diagnosed with ASD and ADHD, as indexed by the Autism Diagnostic Observation Schedule (ADOS). Participants were 209 youth ages 3 to 18 years with ASD, ADHD, Dual Diagnosis (ASD+ADHD) or No Diagnosis. Differences across diagnostic groups were observed for mean communication and social interaction total scores on the ADOS, with the highest scores (i.e., greater impairment) observed for the ASD group and lowest scores for the ADHD and No Diagnosis groups. Results provide the first evidence for use of the ADOS for distinguishing youth who have ADHD alone versus ASD alone or co-occurring ASD+ADHD. Findings are discussed in light of implications for clinical practice and future research.

The ISUT model provides a unique collaboration among the family, educational system, autism experts in the community, and the university medical center autism team while providing a cost-effective means for families to access specialty care while promoting coordination of care within the community.

ObjectivesImmune and stromal cell communication is central in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), however, the nature of these interactions in the synovial pathology of the two pathotypes can differ. Identifying immune-stromal cell crosstalk at the site of inflammation in RA and PsA is challenging. This study creates the first global transcriptomic analysis of the RA and PsA inflamed joint and investigates immune-stromal cell interactions in the pathogenesis of synovial inflammation.MethodsSingle cell transcriptomic profiling of 178 000 synovial tissue cells from five patients with PsA and four patients with RA, importantly, without prior sorting of immune and stromal cells. This approach enabled the transcriptomic analysis of the intact synovial tissue and identification of immune and stromal cell interactions. State of the art data integration and annotation techniques identified and characterised 18 stromal and 14 immune cell clusters.ResultsGlobal transcriptomic analysis of synovial cell subsets identifies actively proliferating synovial T cells and indicates that due to differential λ and κ immunoglobulin light chain usage, synovial plasma cells are potentially not derived from the local memory B cell pool. Importantly, we report distinct fibroblast and endothelial cell transcriptomes indicating abundant subpopulations in RA and PsA characterised by differential transcription factor usage. Using receptor–ligand interactions and downstream target characterisation, we identify RA-specific synovial T cell-derived transforming growth factor (TGF)-β and macrophage interleukin (IL)-1β synergy in driving the transcriptional profile of FAPα+THY1+ invasive synovial fibroblasts, expanded in RA compared with PsA. In vitro characterisation of patient with RA synovial fibroblasts showed metabolic switch to glycolysis, increased adhesion intercellular adhesion molecules 1 expression and IL-6 secretion in response to combined TGF-β and IL-1β treatment. Disrupting specific immune and stromal cell interactions offers novel opportunities for targeted therapeutic intervention in RA and PsA.