IL-3 produced by T cells is crucial for basophil extravasation in hapten-induced allergic contact dermatitis

Carole El Hachem, Pierre Marschall, Pierre Hener, Anupama Karnam, Srinivasa Reddy Bonam, Pierre Meyer, Eric Flatter, Marie Christine Birling, Jagadeesh Bayry, Mei Li

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Basophils have been recognized as a characterized cellular player for Th2 immune responses implicated in allergic diseases, but the mechanisms responsible for basophil recruitment to allergic skin remain not well understood. Using a hapten fluorescein isothiocyanate (FITC)-induced allergic contact dermatitis (ACD) mouse model, we show that basophils in FITC-treated IL-3-knockout mice are defective in crossing the vascular endothelium to enter the inflamed skin. By generating mice in which IL-3 is selectively ablated in T cells, we further demonstrate that IL-3 produced by T cells mediates basophil extravasation. Moreover, basophils sorted from FITC-treated IL-3-knockout mice exhibit a decreased expression of integrins Itgam, Itgb2, Itga2b and Itgb7, which are potentially implicated in extravasation process. Interestingly, we observed that these basophils had a reduced expression of retinaldehyde dehydrogenase 1 family member A2 (Aldh1a2), an enzyme responsible for the production of retinoic acid (RA), and administration of all-trans RA restored partially the extravasation of basophils in IL-3-knockout mice. Finally, we validate that IL-3 induces the expression of ALDH1A2 in primary human basophils, and provide further evidence that IL-3 stimulation induces the expression of integrins particularly ITGB7 in an RA-dependent manner. Together, our data propose a model that IL-3 produced by T cells activates ALDH1A2 expression by basophils, leading to the production of RA, which subsequently induces the expression of integrins crucially implicated in basophil extravasation to inflamed ACD skin.

Original languageEnglish (US)
Article number1151468
JournalFrontiers in immunology
Volume14
DOIs
StatePublished - 2023
Externally publishedYes

Keywords

  • allergy
  • basophil
  • extravasation
  • IL-3
  • integrin
  • retinoic acid
  • skin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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