IL-17A is originally identified as a proinflammatory cytokine that induces neutrophils. Although IL-17A production by CD4+ Th17 T cells is well documented, it is not clear whether IL-17A is produced and participates in the innate immune response against infections. In the present report, we demonstrate that IL-17A is expressed in the liver of mice infected with Listeria monocytogenes from an early stage of infection. IL-17A is important in protective immunity at an early stage of listerial infection in the liver because IL-17A-deficient mice showed aggravation of the protective response. The major IL-17A-producing cells at the early stage were TCR γδ T cells expressing TCR Vγ4 or Vγ6. Interestingly, TCR γδ T cells expressing both IFN-γ and IL-17A were hardly detected, indicating that the IL-17A-producing TCR γδ T cells are distinct from IFN-γ-producing γδ T cells, similar to the distinction between Th17 and Th1 in CD4+ T cells. All the results suggest that IL-17A is a newly discovered effector molecule produced by TCR γδ T cells, which is important in innate immunity in the liver.

Both serum ferritin and anti-MDA5 antibody are powerful indicators for the early diagnosis of A/SIP with DM. Ferritin also predicts disease severity and prognosis for patients with anti-MDA5 antibody. Intensive treatment should be administered to cases that have anti-MDA5 antibody-associated ILD with DM showing hyperferritinaemia, especially if the ferritin level is>or=1600 ng/ml.

Anti-MDA5ab titre and ferritin and IL-18 concentrations are useful for the evaluation of the response to treatment and the status of ILD in patients with anti-MAD5ab-positive DM.

Individuals at high risk of developing seropositive rheumatoid arthritis (RA) can be identified for translational research and disease prevention studies through the presence of highly informative and predictive patterns of RA-related autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in the serum. In serologically positive individuals without arthritis, designated ACPA positive at risk, the presence of mucosal inflammatory processes associated with the presence of local ACPA production has been demonstrated. In other at-risk populations, local RA-related autoantibody production is present even in the absence of serum autoantibodies. Additionally, a proportion of at-risk individuals exhibit local mucosal ACPA production in the lung, as well as radiographic small-airway disease, sputum hypercellularity and increased neutrophil extracellular trap formation. Other mucosal sites in at-risk individuals also exhibit autoantibody production, inflammation and/or evidence of dysbiosis. As the proportion of individuals who exhibit such localized inflammation-associated ACPA production is substantially higher than the likelihood of an individual developing future RA, this finding raises the hypothesis that mucosal ACPAs have biologically relevant protective roles. Identifying the mechanisms that drive both the generation and loss of externally focused mucosal ACPA production and promote systemic autoantibody expression and ultimately arthritis development should provide insights into new therapeutic approaches to prevent RA.

Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience.

No abstract

Although small-scale studies have described the effects of oxytocin on social deficits in autism spectrum disorder (ASD), no large-scale study has been conducted. In this randomized, parallel-group, multicenter, placebo-controlled, double-blind trial in Japan, 106 ASD individuals (18-48 y.o.) were enrolled between Jan 2015 and March 2016. Participants were randomly assigned to a 6-week intranasal oxytocin (48IU/day, n = 53) or placebo (n = 53) group. One-hundred-three participants were analyzed. Since oxytocin reduced the primary endpoint, Autism Diagnostic Observation Schedule (ADOS) reciprocity, (from 8.5 to 7.7; P < .001) but placebo also reduced the score (8.3 to 7.2; P < .001), no between-group difference was found (effect size -0.08; 95% CI, -0.46 to 0.31; P = .69); however, plasma oxytocin was only elevated from baseline to endpoint in the oxytocin-group compared with the placebo-group (effect size -1.12; -1.53 to -0.70; P < .0001). Among the secondary endpoints, oxytocin reduced ADOS repetitive behavior (2.0 to 1.5; P < .0001) compared with placebo (2.0 to 1.8; P = .43) (effect size 0.44; 0.05 to 0.83; P = .026). In addition, the duration of gaze fixation on socially relevant regions, another secondary endpoint, was increased by oxytocin (41.2 to 52.3; P = .03) compared with placebo (45.7 to 40.4; P = .25) (effect size 0.55; 0.10 to 1.0; P = .018). No significant effects were observed for the other secondary endpoints. No significant difference in the prevalence of adverse events was observed between groups, although one participant experienced temporary gynecomastia during oxytocin administration. Based on the present findings, we cannot recommend continuous intranasal oxytocin treatment alone at the current dose and duration for treatment of the core social symptoms of high-functioning ASD in adult men, although this large-scale trial suggests oxytocin's possibility to treat ASD repetitive behavior.

The aim of this study was to evaluate neurological manifestations of primary Sjögren’s syndrome (pSS) and investigate the etiology and pathogenesis of peripheral and central nervous complications in pSS. Thirty-two patients with pSS were enrolled in the present study, 20 of whom had neurological involvement plus sicca symptoms. The clinical features were evaluated by neurological examinations including nerve conduction study, magnetic resonance imaging, cerebrospinal fluid, and electroencephalogram. The frequency of fever was significantly higher (P = 0.006) in pSS with neurological involvement than in pSS without neurological involvement. There was no statistical significance in other factors between the two groups. Peripheral nervous system (PNS), central nervous system (CNS), and both PNS and CNS involvements were revealed in 14, 3, and 3 patients, respectively. Optic neuritis and trigeminal neuralgia were revealed frequently in cranial neuropathy. Anti-aquaporin 4 antibody was detected in one patient with optic neuritis. Of the nine patients with polyneuropathy, eight patients presented pure sensory neuropathy including small fiber neuropathy (SFN). pSS with SFN appeared to have no clinically abnormal features, including muscle weakness and decreasing deep tendon reflex. Skin biopsy revealed epidermal nerve fiber degenerated in one pSS patient with pure sensory neuropathy who was diagnosed as having SFN. Our observations suggest that a number of mechanisms can be attributed to neurological involvements in pSS rather than just the mechanisms previously described (i.e., vasculitis and ganglioneuronitis). Presumably, specific autoantibodies may directly induce injury of the nervous system.