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

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.