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IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease demonstrate a deficiency in this specific regulatory T-cell subpopulation. Tr1 cells are considered an immunosuppressive CD4 T cell population producing IL-10. Here the authors show that IL-10 is insufficient for Tr1 immunosuppression, define surface markers and transcriptional program of the immunosuppressive subset within Tr1, and reveal its deficiency in patients with IBD. [ABSTRACT FROM AUTHOR]

Background and aim Myotonic dystrophy (DM) is a genetic disorder determined by an amplified trinucleotide CTG repeat in the untranslated region of the DMPK gene on chromosome 19q13.3. The incidence of the congenital form is 1 in 47619 live births and the mortality in the neonatal period is up to 40%. Methods: We report a case of congenital DM (CDM, also designated Myotonic Dystrophy Type 1), presented with congenital right diaphragmatic hernia and cerebral bilateral ventricular dilatation, genetically diagnosed. Conclusions: Since no case of congenital diaphragmatic hernia associated with CDM is reported, the present case report could be considered of particular interest.

Since the introduction of biologic response modifiers (BRMs) in the management of children affected by the immune-mediated inflammatory disease, these patients substantially improved their quality of life. BRMs are generally well tolerated and effective in most children and adolescents refractory to conventional immunosuppressive therapy. On the other hand, patients receiving BRMs, especially TNF-α inhibitors, display an increased risk of primary infections or reactivations, i.e. due to Mycobacterium tuberculosis. M. tuberculosis can cause severe disease with consequent short- and long-term morbidity in children on anti-TNF-α treatment. The present paper analyses the increased risk of reactivation of latent tuberculosis infection (LTBI) or de novo TB infection in children treated with TNF-α inhibitors, with the purpose to provide recommendations for screening strategies and safety monitoring of paediatric patients. Special attention is also given to the currently available TB screening tools (IGRAs and TST) and their utility in the diagnosis of LTBI before starting the biologic therapy and during the treatment. Finally, the paper analyses the suggested TB-preventing therapies to adopt in these children and the correct timing to overlap anti-TB and anti-TNF-a treatment.

IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4 + T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3 neg CD4 + T cells that displays regulatory activity unlike other IL-10-producing CD4 + T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4 + T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3 neg CD4 + T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease demonstrate a deficiency in this specific regulatory T-cell subpopulation.