Fatty acid-binding protein 3 controls contact hypersensitivity through regulating skin dermal Vγ4+ γ/δ T cell in a murine model

Shuhei Kobayashi, Hai The Phung, Yoshiteru Kagawa, Hirofumi Miyazaki, Yu Takahashi, Atsuko Asao, Takashi Maruyama, Akihiko Yoshimura, Naoto Ishii, Yuji Owada

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: Fatty acid-binding protein 3 (FABP3) is a cytosolic carrier protein of polyunsaturated fatty acids (PUFAs) and regulates cellular metabolism. However, the physiological functions of FABP3 in immune cells and how FABP3 regulates inflammatory responses remain unclear. Methods: Contact hypersensitivity (CHS) induced by 2,4-dinitrofluorobenzene (DNFB) and fluorescein isothiocyanate was applied to the skin wild-type and Fabp3−/− mice. Skin inflammation was assessed using FACS, histological, and qPCR analyses. The development of γ/δ T cells was evaluated by a co-culture system with OP9/Dll1 cells in the presence or absence of transgene of FABP3. Results: Fabp3-deficient mice exhibit a more severe phenotype of contact hypersensitivity (CHS) accompanied by infiltration of IL-17-producing Vγ4+ γ/δ T cells that critically control skin inflammation. In Fabp3−/− mice, we found a larger proportion of Vγ4+ γ/δ T cells in the skin, even though the percentage of total γ/δ T cells did not change at steady state. Similarly, juvenile Fabp3−/− mice also contained a higher amount of Vγ4+ γ/δ T cells not only in the skin but in the thymus when compared with wild-type mice. Furthermore, thymic double-negative (DN) cells expressed FABP3, and FABP3 negatively regulates the development of Vγ4+ γ/δ T cells in the thymus. Conclusions: These findings suggest that FABP3 functions as a negative regulator of skin inflammation through limiting pathogenic Vγ4+ γ/δ T-cell generation in the thymus.

Original languageEnglish
Pages (from-to)1776-1788
Number of pages13
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume76
Issue number6
DOIs
Publication statusPublished - 2021 Jun

Keywords

  • FABP3
  • contact hypersensitivity
  • skin inflammation
  • γ/δ T-cell development

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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