Selective role of neurokinin B in IL-31–induced itch response in mice

Abstract

US children is in line with data from the single-center population-based birth cohorts from Israel and Spain, reporting cumulative incidence of 0.34% and 0.7%, respectively. 4,5 Our study provides the first-ever estimate of FPIES prevalence in adults. To date, only several small case series of adult patients were published. 2 Our report has several limitations. The survey was not developed to estimate FPIES prevalence, and details of the trigger foods and symptoms are lacking. Although the survey asked about physician-diagnosed FPIES, specific case definition was not provided; we have no information about the diagnostic criteria used, and whether oral food challenges were performed to confirm diagnosis. Therefore, it is possible that FPIES diagnosis was used incorrectly because of the poor familiarity of the physicians with FPIES and led to underestimation or overestimation of true FPIES prevalence. This cross-sectional study captures patients reporting lifetime FPIES; therefore, we do not know which patients may or may not have outgrown FPIES and whether there is any difference in those who do and those who do not outgrow. These data suggest that FPIES affects nearly 1 million people in the United States, and the FPIES prevalence estimates are consistent with reports from Spain and Israel and not greatly different from the Australian estimates. Our data indicate the need for further epidemiologic studies to better characterize the population-level burden of FPIES in the United States.

Interleukin-31 and Pruritic Skin

“…Many pruritogenic axes such as chloroquine/MrgprA3- or histamine/H1R-induced pruritus require natriuretic polypeptide b (Nppb) and gastrin-releasing peptide (GRP) and their respective receptors, natriuretic peptide receptor A (NPRA) and GRP receptor (GRPR), to transmit the sensation of itch in the spinal cord [ 55 , 56 ] ( Figure 2 ). However, IL-31-induced pruritus requires neurokinin B (NKB) instead of Nppb [ 56 ]. NKB binds neurokinin receptor 3 (NK3R) and induces the release of GRP, which mediates the sensation of pruritus [ 56 ] ( Figure 2 ).…”

“…However, IL-31-induced pruritus requires neurokinin B (NKB) instead of Nppb [ 56 ]. NKB binds neurokinin receptor 3 (NK3R) and induces the release of GRP, which mediates the sensation of pruritus [ 56 ] ( Figure 2 ).…”

Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis

“…The transcription factor hypoxia-inducible factor-2α (HIF-2α), also called endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), is required for the production of IL-31 [60]. Binding of IL-31 to IL-31-sensitive dorsal root ganglion cells induces the production of neurokinin B and activates its neurokinin 3 receptor, which then triggers the production of an itch mediator, gastrin-releasing peptide [63]. A recent study also revealed a significant role of P2X3 receptor-positive nerves in chronic pruritus [64].…”

Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch

“…Moreover, the itch responses to subcutaneously injected IL‐31 were significantly attenuated in Nppb ‐KO mice and mice treated with Nppb‐saporin, a toxin that ablated 70% BNP receptor positive neurons in the spinal cord (Mishra & Hoon, ; Pitake et al, ). On the contrary, itch induced by intradermal injection of IL‐31 in mice was not affected by intrathecal injection of Nppb‐saporin and neurokinin B was selectively involved in IL‐31‐induced itch (Sakata et al, ). However, the percentage of the neuronal population ablated is lacking in this later study.…”