Fig. 6: Effect of TRPV1⁺ sensory nerves on the responses of corneal macrophages.

a Cytoscape network analysis of transcripts involved in monocyte chemotaxis, macrophage differentiation, and macrophage activation (up-regulated genes are shown in red and down-regulated genes are shown in green). b–d The gating strategies of flow cytometry for analyzing the number of corneal CCR2⁺ and CCR2^– macrophages (b), production of TNF-α in CCR2⁺ macrophages (c), and production of IL-10 in CCR2^– macrophages (d). e Comparison of the number of CCR2⁺ and CCR2^– macrophages in the cornea between vehicle-treated mice and resiniferatoxin (RTX)-treated mice (n = 3 independent experiments, 5 mice per experiment in each group). f Changes in the production of TNF-α in CCR2⁺ macrophages and IL-10 in CCR2^– macrophages after RTX treatment (n = 3 independent experiments, 8 mice per experiment in each group). g Quantitative polymerase chain reaction (qPCR) analysis of Ramp1 and Sstr1–5 in corneal CCR2⁺ and CCR2^– macrophages (n = 3 independent experiments, 5 mice per experiment in each group). h, i Alteration in the number of CCR2⁺ and CCR2^– macrophages in the cornea after treatment with BIBN 4096 (h, n = 3 independent experiments, 5 mice per experiment in each group) or BIM 23056 (i, n = 3 independent experiments, 5 mice per experiment in each group). j Changes in the production of TNF-α in CCR2⁺ macrophages after BIBN 4096 treatment and IL-10 in CCR2^– macrophages after BIM 23056 treatment (n = 3 independent experiments, 8 mice per experiment in each group). k Difference in the number of CCR2⁺ macrophages (left, n = 3 independent experiments, 5 mice per experiment in each group) and production of TNF-α in CCR2⁺ macrophages (right, n = 3 independent experiments, 8 mice per experiment in each group) among vehicle-treated mice, RTX-treated mice, and RTX-treated mice following calcitonin gene-related peptide (CGRP) treatment. l Difference in the number of CCR2^– macrophages (left, n = 3 independent experiments, 5 mice per experiment in each group) and production of IL-10 in CCR2^–macrophages (right, n = 3 independent experiments, 8 mice per experiment in each group) among vehicle-treated mice, RTX-treated mice, and RTX-treated mice following L-817,818 treatment. Data are presented as mean ± SD. *P < 0.05, **P < 0.01, and ***P < 0.001.