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 gamma/delta 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 V gamma 4(+) gamma/delta T cells that critically control skin inflammation. In Fabp3(-/-) mice, we found a larger proportion of V gamma 4(+) gamma/delta T cells in the skin, even though the percentage of total gamma/delta T cells did not change at steady state. Similarly, juvenile Fabp3(-/-) mice also contained a higher amount of V gamma 4(+) gamma/delta 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 V gamma 4(+) gamma/delta T cells in the thymus. Conclusions: These findings suggest that FABP3 functions as a negative regulator of skin inflammation through limiting pathogenic V gamma 4(+) gamma/delta T-cell generation in the thymus.

Automated summary

The study reveals that FABP3 functions as a negative regulator of skin inflammation by limiting the generation of pathogenic V gamma 4(+) gamma/delta T cells in the thymus.