Transmembrane protein TMEM184B is necessary for interleukin-31-induced itch

Erik G. Larsen, Tiffany S. Cho, Matthew L. McBride, Jing Feng, Bhagyashree Manivannan, Cynthia Madura, Nathaniel E. Klein, Elizabeth B. Wright, Edward S. Wickstead, Hector D. Garcia-Verdugo, Chelsea Jarvis, Rajesh Khanna, Hongzhen Hu, Tally M. Largent-Milnes, Martha R.C. Bhattacharya

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Nociceptive and pruriceptive neurons in the dorsal root ganglia (DRG) convey sensations of pain and itch to the spinal cord, respectively. One subtype of mature DRG neurons, comprising 6% to 8% of neurons in the ganglia, is responsible for sensing mediators of acute itch and atopic dermatitis, including the cytokine IL-31. How itch-sensitive (pruriceptive) neurons are specified is unclear. Here, we show that transmembrane protein 184B (TMEM184B), a protein with roles in axon degeneration and nerve terminal maintenance, is required for the expression of a large cohort of itch receptors, including those for interleukin 31 (IL-31), leukotriene C4, and histamine. Male and female mice lacking TMEM184B show reduced responses to IL-31 but maintain normal responses to pain and mechanical force, indicating a specific behavioral defect in IL-31-induced pruriception. Calcium imaging experiments indicate that a reduction in IL-31-induced calcium entry is a likely contributor to this phenotype. We identified an early failure of proper Wnt-dependent transcriptional signatures and signaling components in Tmem184b mutant mice that may explain the improper DRG neuronal subtype specification. Accordingly, lentiviral re-expression of TMEM184B in mutant embryonic neurons restores Wnt signatures. Together, these data demonstrate that TMEM184B promotes adult somatosensation through developmental Wnt signaling and promotion of proper pruriceptive gene expression. Our data illuminate a new key regulatory step in the processes controlling the establishment of diversity in the somatosensory system.

Original languageEnglish (US)
Pages (from-to)E642-E653
JournalPain
Volume163
Issue number5
DOIs
StatePublished - May 1 2022
Externally publishedYes

Keywords

  • Behavior
  • Development
  • Dorsal root ganglia
  • IL-31
  • Itch
  • Somatosensory
  • Transcriptomics
  • Wnt signaling

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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