SSBD:database v3

386-Takahashi-EarIL31RA

Project

Title

Immunofluorescence images of nerve fiber and IL-31 receptors in the mouse ear skin

Description

IL-31 receptor blockade suppresses pruritus of atopic dermatitis. However, cell-type-specific contributions of IL-31 receptor to itch, its expression mechanism, and the downstream signaling pathway to induce itch remain unknown. In this report, using conditional knockout mice, the authors demonstrate that IL-31-induced itch requires sensory neuronal IL-31 receptor and STAT3. They find that IL-31 receptor expression is dependent on STAT3 in sensory neurons. In addition, pharmacological experiments suggest that STAT3 activation is important for the itch-inducing signaling downstream of the IL-31 receptor. A cutaneous IL-31 injection induces the nuclear accumulation of activated STAT3 first in sensory neurons that abundantly express IL-31 receptor and then in other itch-transmitting neurons. IL-31 enhances itch induced by various pruritogens including even chloroquine. Finally, pruritus associated with dermatitis is partially dependent on sensory neuronal IL-31 receptor and strongly on sensory neuronal STAT3. Thus, sensory neuronal STAT3 is essential for IL-31-induced itch and further contributes to IL-31-independent inflammatory itch.

License

CC BY-NC-ND 4.0

Released at

Oct. 20, 2025, midnight

Updated at

Funding

S.O. was supported by RIKEN Medical Sciences Innovation Hub Pro- gram (RIKEN MIH) and the Special Postdoctoral Researchers program at RIKEN. K.K. is supported by Japan Agency for Medical Research and Develop- ment (AMED) under CREST grant number JP23gm1210006. M.N. is supported by Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under grant number JP21am0101119. K.S. is supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI grant 18H05411. T.O. was supported by AMED under grant number JP18ek0410033 and Japan Science and Technology Agency (JST) under CREST grant number JPMJCR17H1 and is supported by AMED under CREST grant number JP23gm1210006 and JST Moonshot R&D grant number JPMJMS2025.

# of image datasets

10

Papers

Papers

Paper information: Takahashi S, Ochiai S, Jin J, Takahashi N, Toshima S, Ishigame H, Kabashima K, Kubo M, Nakayama M, Shiroguchi K, Okada T. Sensory neuronal STAT3 is critical for IL-31 receptor expression and inflammatory itch. Cell Rep. 2023 Dec 26;42(12):113433.,
Pubmed ID: 38029739,
DOI: https://doi.org/10.1016/j.celrep.2023.113433,
URL: https://pubmed.ncbi.nlm.nih.gov/38029739/

Contacts

Contacts

Takaharu Okada (Imaging Contributor) , Laboratory for Tissue Dynamics , RIKEN IMS
Sonoko Takahashi (Imaging Contributor) , RIKEN IMS
Sotaro Ochiai (Imaging Contributor) , Malaghan Inst Med Res
Noriko Takahashi (Imaging Contributor) , Kansai Med Univ
Susumu Toshima (Imaging Contributor)
Harumichi Ishigame (Imaging Contributor)
Masato Kubo (Imaging Contributor)
Manabu Nakayama (Imaging Contributor) , Kazusa DNA Res Inst

Biosamples

Organisms

Mus musculus (NCBI:txid10090)

Strains

B6.129-Scn10atm2(cre)Jwo/H　　B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J　Il31ra-flox
B6.129-Scn10atm2(cre)Jwo/H　　B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/J

Cells

neuron (CL_0000540)
keratinocyte (CL_0000312)

Cell lines

Ontologies

UBERON

skin of external ear (UBERON_0001459)