Multiple regulatory levels of growth arrest-specific 6 in mucosal immunity against an oral pathogen

Maria Nassar, Yaara Tabib, Tal Capucha, Gabriel Mizraji, Tsipora Nir, Faris Saba, Rana Salameh, Luba Eli-Berchoer, Asaf Wilensky, Tal Burstyn-Cohen*, Avi Hai Hovav

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Growth arrest-specific 6 (GAS6) expressed by oral epithelial cells and dendritic cells (DCs) was shown to play a critical role in the maintenance of oral mucosal homeostasis. In this study, we demonstrate that the induction of pathogen-specific oral adaptive immune responses is abrogated in Gas6-/- mice. Further analysis revealed that GAS6 induces simultaneously both pro-and anti-inflammatory regulatory pathways upon infection. On one hand, GAS6 upregulates expression of adhesion molecules on blood vessels, facilitating extravasation of innate inflammatory cells to the oral mucosa. GAS6 also elevates expression of CCL19 and CCL21 chemokines and enhances migration of oral DCs to the lymph nodes. On the other hand, expression of pro-inflammatory molecules in the oral mucosa are downregulated by GAS6. Moreover, GAS6 inhibits DC maturation and reduces antigen presentation to T cells by DCs. These data suggest that GAS6 facilitates bi-directional trans-endothelial migration of inflammatory cells and DCs, whereas inhibiting mucosal activation and T-cell stimulation. Thus, the orchestrated complex activity of GAS6 enables the development of a rapid and yet restrained mucosal immunity to oral pathogens.

Original languageAmerican English
Article number1374
JournalFrontiers in Immunology
Volume9
Issue numberJUN
DOIs
StatePublished - 18 Jun 2018

Bibliographical note

Publisher Copyright:
© 2018 Nassar, Tabib, Capucha, Mizraji, Nir, Saba, Salameh, Eli-Berchoer, Wilensky, Burstyn-Cohen and Hovav.

Keywords

  • Growth arrest-specific 6
  • Immunoregulation
  • Infection
  • Mucosa
  • Oral

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