CCL28 Is Involved in Mucosal IgA Responses, Olfaction, and Resistance to Enteric Infections

J Interferon Cytokine Res. 2019 Apr;39(4):214-223. doi: 10.1089/jir.2018.0099. Epub 2019 Mar 11.

Abstract

CCL28 is a mucosal chemokine that has been involved in various responses, including IgA production. We have analyzed its production in human tissues using a comprehensive microarray database. Its highest expression is in the salivary gland, indicating that it is an important component of saliva. It is also expressed in the trachea, bronchus, and in the mammary gland upon onset of lactation. We have also characterized a Ccl28-/- mouse that exhibits very low IgA levels in milk, and the IgA levels in feces are also reduced. These observations confirm a role for the CCL28/CCR10 chemokine axis in the recruitment of IgA plasmablasts to the lactating mammary gland. CCL28 is also expressed in the vomeronasal organ. We also detected olfactory defects (anosmia) in a Ccl28-/- mouse suggesting that CCL28 is involved in the function/development of olfaction. Importantly, Ccl28-/- mice are highly susceptible to Salmonella enterica serovar Typhimurium in an acute model of infection, indicating that CCL28 plays a major role in innate immunity against Salmonella in the gut. Finally, microbiome studies revealed modest differences in the gut microbiota between Ccl28-/- mice and their cohoused wild-type littermates. The latter observation suggests that under homeostatic conditions, CCL28 plays a limited role in shaping the gut microbiome.

Keywords: chemokines; gut; innate immunity; vomeronasal organ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Chemokines, CC / immunology*
  • Chemokines, CC / physiology*
  • Gastrointestinal Microbiome / immunology
  • Homeostasis / immunology
  • Immunity, Innate / immunology*
  • Immunity, Mucosal / immunology*
  • Immunoglobulin A / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Salmonella Infections, Animal / immunology*
  • Salmonella Infections, Animal / microbiology
  • Salmonella enterica / immunology
  • Smell / physiology*

Substances

  • Ccl28 protein, mouse
  • Chemokines, CC
  • Immunoglobulin A