Fig. 7: Interaction of nociceptive neurons with CAFs to suppress NK cells.

a Visualization of specific differences in the IL-15 signaling pathway between vehicle and RTX groups. The marked networks represent signal transmission and communication between cell subsets, and the signal intensity between cells is reflected by the thickness of the lines. b Visualization of cell communication signals: output signals between vehicle and RTX groups. The horizontal coordinate represents each cell group, and the vertical coordinate represents the top-ranked signaling molecules. The darker green in the heat map represents an increase in signal intensity. The histograms on the upper and right sides represent the summation of signal intensities. c Change of proliferaton of NK cells when treated with the culture or co-culture medium of DRG neuron, mPSC-v, Ramp1 KO mPSC, or IL-15 KO mPSC for 24 h (n = 5 cultures/group). d Expression of NK cell activation markers including TNF-α and GrzmB after the indicated co-incubation with culture medium by flow cytometry (n = 5 cultures/group). e Levels of NGF released from PSC or PSC co-cultured with DRG neurons (n = 5 cultures/group). f Levels of NGF in mPSC after vehicle, CGRP (1 nM) treatment or CGRP plus Rimegepant (Rime, 1 μM) treatment (n = 5 cultures/group). g NGF level in the co-culture medium of DRG neurons with mPSC-v or Ramp1 KO mPSC (n = 5 cultures/group). h Level of CGRP in DRG neurons after stimulation with increasing concentrations of NGF (n = 5 cultures/group). i Level of CGRP released from DRG neurons cultured alone or co-cultured with mPSCs or with mPSCs plus TrkA inhibitor (1 μM) for 24 h (n = 5 cultures/group). j Concentration of CGRP released from DRG neurons co-cultured with mPSC-v or Ngf KO mPSC for 24 h (n = 5 cultures/group). k Representative images of neurite outgrowth of DRGs treated with mPSC conditioned medium (left) and quantification of total length of neurites extending from DRG (right; n = 3 culture/group). Scale bar, 100 μm. Data are shown as mean ± SEM; *P < 0.05, **P < 0.01, ***P < 0.001.