Immunity to commensal skin fungi promotes psoriasiform skin inflammation

Under steady-state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiotaspecific T cells contributes to tissue pathologies...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2020-07, Vol.117 (28), p.16465-16474
Hauptverfasser: Hurabielle, Charlotte, Link, Verena M., Bouladoux, Nicolas, Han, Seong-Ji, Merrill, Eric Dean, Lightfoot, Yaima L., Seto, Nickie, Bleck, Christopher K. E., Smelkinson, Margery, Harrison, Oliver J., Linehan, Jonathan L., Tamoutounour, Samira, Lionakis, Michail S., Kaplan, Mariana J., Nakajima, Saeko, Belkaid, Yasmine
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Sprache:eng
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Zusammenfassung:Under steady-state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiotaspecific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi preexposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2003022117