David Sleurs

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.

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.

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.