Fig 2: FGF21 alleviation of C. acnes-induced TLR2 in mouse ears. (A) Protein expression levels of TLR2 in C. acnes-stimulated mouse ears with and without FGF21 treatment (n = 6 mice/group). (B) Quantification of Tlr2 mRNA level in the ears of mice treated with FGF21 after C. acnes stimulation. (n = 5 mice/group). (C,D) Representative confocal scans are shown for TLR2 (red) and CD11b (green), and the nuclei are stained with DAPI (blue) (n = 6 mice/group). Scale bar = 100 µm. All data are presented as the mean ± the SD; ** p < 0.01, and *** p < 0.001.

Fig 3: FGF21 ameliorates C. acnes-induced TLR2 activities in HaCaT cells. (A,B) The time points included 0, 3, 6, 12, 24, and 48 h after stimulating with C. acnes at the density of 1 × 107 CFU/mL. The protein expression level of TLR2 was detected and analyzed in C. acnes-stimulated HaCaT cells with and without FGF21 treatment (20 ng/mL). (C) Quantification of TLR2 mRNA level in HaCaT cells subjected to control, C. acnes stimulation, or FGF21 treatment. (D) Representative confocal scans are shown for TLR2 (red), and the nuclei are stained with DAPI (blue). Scale bar = 100 µm. All data are presented as the mean ± the SD; * p < 0.05, ** p < 0.01, and *** p < 0.001; n.s., non-significant.

Fig 4: Proposed mechanism of action of FGF21 in C. acnes-induced skin disease. Under the induction of C. acnes, FGF21 secreted from fibroblasts inhibits TLR2, NF-KB, and MAPK signaling and inflammatory factors in keratinocytes by activating FGFR1 and KLB, and exogenous treatment by FGF21 can also relieve a series of inflammatory reactions induced by C. acnes.

Fig 5: FGF21 suppresses C. acnes-induced inflammation by inhibiting TLR2/NF-?B/MAPK signaling pathways in mouse ears. (A) Protein expression levels of p65 and I?B in C. acnes-stimulated mouse ears with and without FGF21 treatment (n = 6 mice/group). (B) The nuclear and cytosolic fractions of p65 assayed by Western blotting (n = 6 mice/group). (C) Representative confocal scans are shown for p65 (red), and the nuclei are stained with DAPI (blue) (n = 6 mice/group). Scale bar = 50 µm. (D) Protein expression levels of JNK and p38 in C. acnes-stimulated mouse ears with and without FGF21 treatment (n = 6 mice/group). All data are presented as the mean ± the SD; ** p < 0.01, and *** p < 0.001.