Open AccessSkin-resident dendritic cells mediate postoperative pain via CCR4 on sensory neurons
Author(s) -
Jaqueline Raymondi Silva,
Mircea Iftinca,
Francisco Isaac Fernandes Gomes,
Julia P. Segal,
Olivia M. A. Smith,
Courtney A. Bannerman,
Atlante S. Mendes,
Ma Defaye,
Madeline Robinson,
Ian Gilron,
Thiago Mattar Cunha,
Christophe Altier,
Nader Ghasemlou
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2118238119
Subject(s) - ccr4 , ccl17 , chemokine , immunology , medicine , immune system , chemokine receptor , pharmacology
Significance Interactions between the nervous and immune systems control the generation and maintenance of inflammatory pain. However, the immune cells and mediators controlling this response remain poorly characterized. We identified the cytokines CCL22 and CCL17 as secreted mediators that act directly on sensory neurons to mediate postoperative pain via their shared receptor, CCR4. We also show that skin-resident dendritic cells are key contributors to the inflammatory pain response. Blocking the interaction between these dendritic cell–derived ligands and their receptor can abrogate the pain response, highlighting CCR4 antagonists as potentially effective therapies for postoperative pain. Our findings identify functions for these tissue-resident myeloid cells and uncover mechanisms underlying pain pathophysiology.