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Pathogenic CD8 T cell responses are driven by neutrophil-mediated hypoxia in cutaneous leishmaniasis. | LitMetric

AI Article Synopsis

Article Abstract

Cutaneous leishmaniasis caused by parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we find that expression of the cytolytic effector molecule granzyme B is restricted to lesional CD8 T cells in - infected mice, suggesting that local cues within inflamed skin induce cytolytic function. Expression of Blimp-1 ( ), a transcription factor necessary for cytolytic CD8 T cell differentiation, is driven by hypoxia within the inflamed skin. Hypoxia is further enhanced by the recruitment of neutrophils that consume oxygen to produce reactive oxygen species, ultimately increasing granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibit hypoxia transcription signatures that correlate with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614852PMC
http://dx.doi.org/10.1101/2023.10.18.562926DOI Listing

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