TRPV4-mediated detection of hyposmotic stress by skin keratinocytes activates developmental immunity

Jorge Galindo-Villegas, Ana Montalban-Arques, Sergio Liarte, Sofia De Oliveira, Carlos Pardo-Pastor, Fanny Rubio-Moscardo, Jose Meseguer, Miguel A. Valverde, Victoriano Mulero

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


As an organism is exposed to pathogens during very early development, specific defense mechanisms must take effect. In this study, we used a germ-free zebrafish embryo model to show that osmotic stress regulates the activation of immunity and host protection in newly hatched embryos.Mechanistically, skin keratinocytes were responsible for both sensing the hyposmolarity of the aquatic environment and mediating immune effector mechanisms. This occurred through a transient potential receptor vanilloid 4/Ca2+/TGF-β-activated kinase 1/NF-κB signaling pathway. Surprisingly, the genes encoding antimicrobial effectors, which do not have the potential to cause tissue damage, are constitutively expressed during development, independently of both commensal microbes and osmotic stress. Our results reveal that osmotic stress is associated with the induction of developmental immunity in the absence of tissue damage and point out to the embryo skin as the first organ with full capacities to mount an innate immune response.

Original languageEnglish (US)
Pages (from-to)738-749
Number of pages12
JournalJournal of Immunology
Issue number2
StatePublished - Jan 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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