Highlights d Platelets sequester pro-and anti-inflammatory cytokines released by monocytes d In the presence of LPS, platelets skew monocytes toward a pro-inflammatory phenotype d During sepsis, platelet transfusion increases iNOS + macrophages and bacterial clearance d Platelet transfusion increases septic mice survival in a narrow time frame
Langerhans cell histiocytosis (LCH) is a rare disease with an unknown etiology characterized by heterogeneous lesions containing CD207CD1a cells that can arise in almost any tissue and cause significant morbidity and mortality. Precursors of pathological Langerhans cells have yet to be defined. Our aim was to identify circulating CD207CD1a cells and their inducers in LCH. Expression of CD207 and CD1a in the blood myeloid compartment as well as thymic stromal lymphopoietin (TSLP) and transforming growth factor β (TGF-β) plasma levels were measured in 22 pediatric patients with active disease (AD) or nonactive disease (NAD). In patients with AD vs those with NAD, the myeloid compartment showed an increased CD11b (CD11b plus CD11b) fraction (39.7 ± 3.6 vs 18.6 ± 1.9), a higher percentage of circulating CD11bCD11cCD207 cells (44.5 ± 11.3 vs 3.2 ± 0.5), and the presence of CD11cCD207CD1a cells (25.0 ± 9.1 vs 2.3 ± 0.5). Blood CD207CD1a cells were not observed in adult controls or umbilical cord. Increased TSLP and TGF-β levels were detected in patients with AD. Interestingly, plasma from patients with AD induces CD207 expression on CD14 monocytes. We conclude that CD207CD1a cells are circulating in patients with active LCH, and TSLP and TGF-β are potential drivers of Langerhans-like cells in vivo.
Multiple sclerosis (MS) is a highly disabling neurodegenerative autoimmune condition in which an unbalanced immune response plays a critical role. Although the mechanisms remain poorly defined, helminth infections are known to modulate the severity and progression of chronic inflammatory diseases. The tyrosine kinase receptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immune response in various inflammatory settings. We show here that patients with concurrent natural helminth infections and MS condition (HIMS) had an increased expression of the negative regulatory TAM receptors in antigen-presenting cells and their agonist GAS6 in circulating CD11bhigh and CD4+ T cells compared to patients with only MS. The Th17 subset was reduced in patients with HIMS with a subsequent downregulation of its pathogenic genetic program. Moreover, these CD4+ T cells promoted lower levels of the co-stimulatory molecules CD80, CD86, and CD40 on dendritic cells compared with CD4+ T cells from patients with MS, an effect that was GAS6-dependent. IL-10+ cells from patients with HIMS showed higher GAS6 expression levels than Th17 cells, and inhibition of phosphatidylserine/GAS6 binding led to an expansion of Th17 effector genes. The addition of GAS6 on activated CD4+ T cells from patients with MS restrains the Th17 gene expression signature. This cohort of patients with HIMS unravels a promising regulatory mechanism to dampen the Th17 inflammatory response in autoimmunity.
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