STING-mediated neutrophil recruitment in DRG: A potential driver of alloknesis in atopic dermatitis

Summary: Alloknesis, an abnormal itch response to non-pruritic stimuli, is a common symptom of atopic dermatitis (AD). Recent research suggests that neutrophil accumulation in the dorsal root ganglion (DRG) contributes to sensory hypersensitivity, including mechanical allodynia. However, the precise mechanisms underlying alloknesis in AD remain unclear. Our previous findings demonstrated a significant increase in STING expression in DRG neurons, along with increased neutrophil infiltration of the DRG in AD mice. In this study, we investigated whether STING activation in DRG neurons induces neutrophil activation and recruitment, contributing to alloknesis. In AD mice, <i>STING</i> mRNA levels in the DRG were positively correlated with clinical severity, neutrophil infiltration, and neutrophil extracellular trap (NET)-related gene expression. Among these, cathepsin G (<i>Ctsg</i>) mRNA expression showed a strong correlation with pruritic behavior, suggesting its role in itch modulation. Moreover, intrathecal administration of the STING agonist ADU-S100 induced alloknesis and significantly increased neutrophil infiltration in the DRG, along with upregulation of NET-associated genes. Notably, alloknesis scores were positively correlated with neutrophil infiltration and the mRNA levels of <i>Il6</i> and <i>Ctsg</i> in the DRG. Furthermore, neutrophil migration assays demonstrated that supernatants from cultured DRG neurons treated with ADU-S100 induced neutrophil chemotaxis in a concentration-dependent manner. These findings suggest that STING activation in DRG neurons drives neutrophil recruitment and activation, contributing to alloknesis in AD. Further research into neuro-neutrophil interactions in the DRG may provide new insights into itch sensitization in AD and serve as a potential therapeutic target for chronic itch. Young Su Jang¹, Jae-sang Ryu², Hyeongjin Na³, Hai vin Kim², Da Hye Seo², Dong Hyun Kim², Jung U Shin² 1. Biomedical Science, CHA University, Pocheon-si, Gyeonggi-do, Korea (the Republic of). 2. Dermatology, CHA University Bundang Medical Center, Seongnam-si, Gyeonggi-do, Korea (the Republic of). 3. Medicine, CHA University, Pocheon-si, Gyeonggi-do, Korea (the Republic of). Cell Communication Networks and Stromal Biology