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  • Title: Neutrophil extracellular traps and their histones promote Th17 cell differentiation directly via TLR2.
    Author: Wilson AS, Randall KL, Pettitt JA, Ellyard JI, Blumenthal A, Enders A, Quah BJ, Bopp T, Parish CR, Brüstle A.
    Journal: Nat Commun; 2022 Jan 26; 13(1):528. PubMed ID: 35082281.
    Abstract:
    Neutrophils perform critical functions in the innate response to infection, including through the production of neutrophil extracellular traps (NETs) - web-like DNA structures which are extruded from neutrophils upon activation. Elevated levels of NETs have been linked to autoimmunity but this association is poorly understood. By contrast, IL-17 producing Th17 cells are a key player in various autoimmune diseases but are also crucial for immunity against fungal and bacterial infections. Here we show that NETs, through their protein component histones, directly activate T cells and specifically enhance Th17 cell differentiation. This modulatory role of neutrophils, NETs and their histones is mediated downstream of TLR2 in T cells, resulting in phosphorylation of STAT3. The innate stimulation of a specific adaptive immune cell subset provides an additional mechanism demonstrating a direct link between neutrophils, NETs and T cell autoimmunity.
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