Dataset Fig1B_IL31RA_ctrl_1
Project
386-Takahashi-EarIL31RA
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.
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.
Title
Z-series immunofluorescence images of the ear skin from control mouse
Description
Z-series immunofluorescence images of the ear skin from control mouse. The skin was stained with anti-IL31 RA (Interleukin 31 Receptor A), and DAPI. tdTomato-labeled sensory neuron fibers heavily innervate the epidermis, wheres there are almost no IL-31 RA-positive nerves found in the epidermis.
Chennel1;DAPI, Channel2;IL31-RA, Channel3;tdTomato,
Channel4;βIII-tubulin
Description
Mouse ear pinnae were harvested and split into dorsal and ventral layers. The ventral layer with the cartilage was used to whole mount immunofluorescence staining of ear skin tissue.
Intrinsic variables
C- and A-delta-fiber sensory neurons were labeled with tdTomato
Gene ontology: Biological processes
Gene ontology: Cellular components
Gene ontology: Molecular functions
Protein names
Interleukin-31 receptor subunit alpha (
Q8K5B1)
βIII-tubulin (
Q9ERD7)
Dimensions
512x512x94x4x1
Detection methods
photomultiplier tube (PMT)
Visualization methods
DAPI
Alexa Flour 488
Alexa Flour 555
Alexa Flour 647
Illumination methods
photomultiplier tube (PMT)
Contrast enhancing methods
optical method
Resolution enhancing methods
Sample preparation methods
4% PFA fixed whole mounted tissue
Light source
405-nm diode laser, 488-nm OPSL, a 552-nm OPSL, 638-nm diode laser
Objective
HC PL APO CS2 40x/1.30 OIL lens
Filter set
414–448nm emission filter for DAPI; 498-538nm emission filter for Alexa Flour 488; 555-597nm emission filter for Alexa Flour 555; 653–800nm emission filter for Alexa Flour 647