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Detail of Fig1B_IL31RA_ctrl_4

Sonoko Takahashi, Sotaro Ochiai, Jianshi Jin, Noriko Takahashi, Susumu Toshima, Harumichi Ishigame, Kenji Kabashima, Masato Kubo, Manabu Nakayama, Katsuyuki Shiroguchi, Takaharu Okada (2023) Sensory neuronal STAT3 is critical for IL-31 receptor expression and inflammatory itch., Cell reports, pp. 113433

Published in 2023 Nov 15 (Electronic publication in Nov. 15, 2023, midnight )

• doi: 10.1016/j.celrep.2023.113433
• pmid: 38029739
  

(Abstract) 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. Here, using conditional knockout mice, we demonstrate that IL-31-induced itch requires sensory neuronal IL-31 receptor and STAT3. We 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.