Tissue-restricted control of established central nervous system autoimmunity by TNF receptor 2-expressing Treg cells.

CD4+Foxp3+ regulatory T (Treg) cells are central modulators of autoimmune diseases. However, the timing and location of Treg cell-mediated suppression of tissue-specific autoimmunity remain undefined. Here, we addressed these questions by investigating the role of tumor necrosis factor (TNF) receptor 2 (TNFR2) signaling in Treg cells during experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. We found that TNFR2-expressing Treg cells were critical to suppress EAE at peak disease in the central nervous system but had no impact on T cell priming in lymphoid tissues at disease onset. Mechanistically, TNFR2 signaling maintained functional Treg cells with sustained expression of CTLA-4 and Blimp-1, allowing active suppression of pathogenic T cells in the inflamed central nervous system. This late effect of Treg cells was further confirmed by treating mice with TNF and TNFR2 agonists and antagonists. Our findings show that endogenous Treg cells specifically suppress an autoimmune disease by acting in the target tissue during overt inflammation. Moreover, they bring a mechanistic insight to some of the adverse effects of anti-TNF therapy in patients.

MAIT cells detect and efficiently lyse bacterially-infected epithelial cells.

Mucosal associated invariant T cells (MAIT) are innate T lymphocytes that detect a large variety of bacteria and yeasts. This recognition depends on the detection of microbial compounds presented by the evolutionarily conserved major-histocompatibility-complex (MHC) class I molecule, MR1. Here we show that MAIT cells display cytotoxic activity towards MR1 overexpressing non-hematopoietic cells cocultured with bacteria. The NK receptor, CD161, highly expressed by MAIT cells, modulated the cytokine but not the cytotoxic response triggered by bacteria infected cells. MAIT cells are also activated by and kill epithelial cells expressing endogenous levels of MRI after infection with the invasive bacteria Shigella flexneri. In contrast, MAIT cells were not activated by epithelial cells infected by Salmonella enterica Typhimurium. Finally, MAIT cells are activated in human volunteers receiving an attenuated strain of Shigella dysenteriae-1 tested as a potential vaccine. Thus, in humans, MAIT cells are the most abundant T cell subset able to detect and kill bacteria infected cells.

Psychotic-like experiences are associated with physical disorders in general population: A cross-sectional study from the NESARC II.

BACKGROUND: Psychotic-like experiences (PLEs) constitute subthreshold symptoms of psychotic disorders, and belong to five distinct dimensions: Positive, Negative, Depressive, Mania and Disorganization. PLEs are associated with various psychiatric disorders. However, few studies examined their association with physical disorders. OBJECTIVE: Our aims were (1) to assess the associations between various physical disorders and PLEs in a U.S. representative sample, and (2) to examine these associations according to the five dimensions of PLEs. METHOD: We used data from the wave II (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-II), a large national sample representative of the US population (N = 34,653). Participants were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule 4. Twenty-two PLEs were examined. Lifetime prevalence and adjusted Odds-Ratio (aOR) reflecting the association of sixteen physical disorders (including notably metabolic conditions and heart diseases) with PLEs were calculated. RESULTS: All studied physical disorders were associated with the presence of PLEs. Particularly the presence of any physical condition, any heart disease and diabetes were more frequent in participants with at least one PLE compared with the group without any PLE (aOR = 1.74, 95% CI = 1.62-1.87, aOR = 1.44, 95% CI = 1.33-1.55 and aOR = 1.38, 95% CI = 1.24-1.54, respectively). Almost all physical disorders were associated with the five dimensions of PLEs. CONCLUSIONS: PLEs were associated with a large range of physical disorders, with a gradual dose effect. To assess PLEs in the general population could help with the screening of subjects with physical disorders.

The association of stroke with mental and physical disorders in US adults: A nationally representative study.

Stroke has been linked to various physical and mental disorders, with both stroke and its comorbidities significantly impacting public health. In this population-based study, we evaluate the relationships between stroke, physical conditions, mental disorders, and their effect on quality of life. Data were gathered from a nationally representative sample of 36,309 civilian participants aged 18 years and older in the National Epidemiologic Survey on Alcohol and Related Conditions-III. We examined the prevalence of past-year stroke, its sociodemographic characteristics, and its associations with past-year mental disorders (according to the DSM-5) and physical conditions. Furthermore, we explored the connections between stroke and health-related quality of life, accounting for comorbidities. The past 12-month stroke prevalence was estimated at 0.82%. Participants with stroke exhibited a significantly higher past 12-month mental disorder prevalence than those without stroke. Specifically, individuals with stroke faced a higher risk of mood disorders, anxiety disorders, tobacco use disorder, and opioid use disorder compared to those without stroke. Stroke was also positively associated with 24 out of the 27 physical conditions assessed in this study. Participants with stroke experienced lower mental and physical quality of life compared to those without stroke. Stroke was significantly related to numerous mental and physical disorders. The association of stroke with diminished health-related quality of life was not only mediated by these comorbidities but should also be considered as inherently linked to stroke itself.

Psychotic-like experiences in general population: Psychiatric comorbidity and impact on quality of life across lifespan.

BACKGROUND AND HYPOTHESIS: In this study, we aimed to determine the prevalence of Psychotics-Like Experiences according to age group and their association with psychiatric disorders through these different age-group, as well as their impact on quality of life. STUDY DESIGN: Using data from the second wave of the NESARC, a large general population study, we considered 6 mutually exclusive groups according to the age at the interview: 20-29 years; 30-39 years; 40-49 years; 50-59 years; 60-69 years; 70+ years. We determined the frequency of PLEs defined as positive, negative, depressive, mania and disorganization symptoms with reference to the PANSS, and the association between the presence of PLEs in the previous year and the presence of lifetime psychiatric disorders and quality of life across different age groups. STUDY RESULTS: The prevalence of PLEs decreased across age from a 34.7 % in the 20-29 years age group, to 19.7 % in the 70+ years age group. Across all age groups, individuals who reported PLEs in the previous year had higher risk of having any psychiatric disorder, (i.e any mood disorder, any anxiety disorder any substance abuse and any personality disorder) compared to individuals not reporting PLEs. All dimensions of quality of life on the SF12 scale were negatively associated with the presence of a PLE regardless of age group. CONCLUSION: We found that the frequency of PLEs decreased with age and that the presence of PLE is associated with psychiatric disorders and with impaired quality of life in all age groups.

Comorbidities of self-reported fibromyalgia in United States adults: A cross-sectional study from The National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III).

BACKGROUND: Fibromyalgia has been associated with various physical and mental disorders. However, these comorbidities need to be quantified in a population-based study. METHOD: We compared participants with and without self-reported fibromyalgia to assess (a) The prevalence of self-reported fibromyalgia and its sociodemographic characteristics in a US representative sample, (b) The associations between self-reported fibromyalgia and lifetime and past 12-month mental and physical disorders and (c) The quality of life associated with self-reported fibromyalgia. This cross-sectional study used a large national sample (n = 36,309) of the US population, the National Epidemiologic Survey on Alcohol and Related Conditions-III. Face to face interviews were conducted, collecting sociodemographic characteristics, diagnostic and statistical manual of mental disorders-5 structured diagnosis and self-reported medical conditions (including fibromyalgia). RESULTS: The past 12-month prevalence of self-reported fibromyalgia was estimated at 2.05%. Participants with self-reported fibromyalgia were significantly at higher risk to report a lifetime history of mental disorder (adjusted odds ratio [aOR] = 2.32). Self-reported fibromyalgia was also positively associated with 24 of the 27 physical conditions assessed in this study. Participants with self-reported fibromyalgia were more likely to report a past 12-month history of suicide attempts (aOR = 5.81), substance use disorders (aOR = 1.40), mood disorders (aOR = 2.67), anxiety disorders (aOR = 2.75) and eating disorders (aOR = 2.45). Participants with self-reported fibromyalgia had lower levels of both mental and physical quality of life than those without fibromyalgia. CONCLUSIONS: Participants with self-reported fibromyalgia have a higher prevalence of comorbid mental and physical disorders, and lower mean levels of mental and physical quality of life than their counterparts without fibromyalgia. SIGNIFICANCE: We showed here a strong association of self-reported fibromyalgia with both mental and physical comorbidities. We showed that among participants with self-reported fibromyalgia, more than 8 out of 10 had at least three other physical comorbidities, and almost half had at least three mental comorbidities. This is a cross-sectional study using a representative sample of the US population with highly reliable psychiatric diagnosis that makes our results generalizable. Practitioners managing fibromyalgia should search and treat these comorbidities.