Frontline Science: Nasal epithelial GM-CSF contributes to TLR5-mediated modulation of airway dendritic cells and subsequent IgA response

Journal of Leukocyte Biology
Yuan CaoHuimin Yan

Abstract

Flagellin, as a TLR5 agonist, is an established mucosal adjuvant for enhancing mucosal IgA responses by i.n. immunization. Nasal epithelial cells (NECs) are the first sentinel cells to be exposed to antigen and adjuvant in i.n. immunization, and it is suggested that they play an important role in the mucosal adjuvant activity of flagellin. However, the molecular mechanism leading to modulation and the response by flagellin-activated NECs remain unknown. We aimed to identify the soluble mediator(s) from flagellin-activated NECs that modulate the functions of airway dendritic cells (DCs) and enhance subsequent IgA response. In vitro studies showed that compared with the TLR4 agonist LPS, flagellin directly triggered slight up-regulation of CD80 on airway DCs but was insufficient to affect CD86 expression and DC-mediated IgA response. With the use of an in vitro system for culturing mouse primary NECs (mNECs), we demonstrated that flagellin-activated mNECs could functionally modulate airway DCs, which manifested as significant up-regulation of CD80/CD86 and enhancement of IgA production. The functional modulation of airway DCs was dependent on TLR5 activation of mNECs rather than direct TLR5 activation of airway DCs. With the use ...Continue Reading

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Citations

Nov 21, 2017·Cellular & Molecular Immunology·Jingyi Yang, Huimin Yan
Aug 29, 2017·Cellular & Molecular Immunology·Maohua ZhongYaoming Li
May 12, 2020·Journal of Medical Virology·Chiranjib ChakrabortyGovindasamy Agoramoorthy
Sep 2, 2017·Journal of Leukocyte Biology·Michael P Cancro, David M Allman
Oct 4, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aneesh VijayanJean-Claude Sirard
Feb 9, 2021·BioMed Research International·Huihui ZhangYuanyi Peng

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