The Long Pentraxin 3 (PTX3) Suppresses Immunity to Cutaneous Leishmaniasis by Regulating CD4+ T Helper Cell Response

Autor: Gaurav Gupta, Zhirong Mou, Ping Jia, Rohit Sharma, Romaniya Zayats, Sayonara M. Viana, Lianyu Shan, Aldina Barral, Viviane S. Boaventura, Thomas T. Murooka, Abdel Soussi-Gounni, Camila I. de Oliveira, Jude E. Uzonna
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cell Reports, Vol 33, Iss 11, Pp 108513- (2020)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2020.108513
Popis: Summary: The long pentraxin 3 (PTX3) plays a critical role in inflammation, tissue repair, and wound healing. Here, we show that PTX3 regulates disease pathogenesis in cutaneous leishmaniasis (CL). PTX3 expression increases in skin lesions in patients and mice during CL, with higher expression correlating with severe disease. PTX3-deficient (PTX3−/−) mice are highly resistant to L. major and L. braziliensis infections. This enhanced resistance is associated with increases in Th17 and IL-17A responses. The neutralization of IL-17A abolishes this enhanced resistance, while rPTX3 treatment results in decrease in Th17 and IL-17A responses and increases susceptibility. PTX3−/− CD4+ T cells display increased differentiation to Th17 and expression of Th17-specific transcription factors. The addition of rPTX3 suppresses the expression of Th17 transcription factors, Th17 differentiation, and IL-17A production by CD4+ T cells from PTX3−/− mice. Collectively, our results show that PTX3 contributes to the pathogenesis of CL by negatively regulating Th17 and IL-17A responses.
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