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. 2024 Dec;79(12):3537-3539.
doi: 10.1111/all.16260. Epub 2024 Jul 26.

Anaplastic lymphoma kinase as a new therapeutic target in inflammatory itch

Tiphaine Voisin  1 , Elodie Labit  1 , Nicolas Gaudenzio  1   2 , Lilian Basso  1
Affiliations

Anaplastic lymphoma kinase as a new therapeutic target in inflammatory itch

Tiphaine Voisin et al. Allergy. 2024 Dec.
No abstract available

PubMed Disclaimer

Conflict of interest statement

NG is (or was) collaborating or consulting or member of scientific advisory board for Genoskin (CSO, shareholder), Escient Pharmaceuticals, Aikium, CEVA, MaxiVax, Boehringer Ingelheim, Novartis, Sanofi, ArgenX.

Figures

FIGURE 1
FIGURE 1
Increased expression of Alkal2 and pAlk during skin inflammation. (A) Induced genes in sensory neurons in AD‐model (MC903) and CHS‐model (Oxazolone, oxa). (B) Alkal2 mRNA expression in DRGs in DNFB (n = 12–13, three independent experiments) and MC903 (n = 5–7, two independent experiments) models. (C) Spinal dorsal horn (SDH) labeled with pAlk (red), IB4 (green) and DAPI (white) in MC903‐ (up) and DNFB‐ (down) induced skin inflammation (scale = 100 μm). (D) Number of pALK positive cells within the SDH in MC903 (up) and DNFB (down) models of skin inflammation (MC903: n = 5–7; DNFB: n = 7–11, from two independent experiments). (E, G) UMAP representation of spinal cord neurons from mouse (E) and human (G). (F, H) Expression density of Grpr (up) and Alk (down) in mouse (F) and human (H). Values as mean ± SEM, *<0.05, Mann–Whitney t test.
FIGURE 2
FIGURE 2
Inhibition of Alk ameliorates DNFB‐induced inflammatory itch in mice. (A) Diagram of lorlatinib (1 mg/mL) gavage procedure during DNFB‐induced CHS. (B) Effect of lorlatinib treatment on the development of itch at Day 0–3 of the DNFB model (D0–D2, n = 10, from two independent experiments and D3, n = 24 from four independent experiments). (C) Skin pathology score (n = 10, from two independent experiments) and (D) percentage of increase in the skin thickness (n = 9–10, from two independent experiments) in vehicle and lorlatinib treated on Day 4 of DNFB. (E) Representative pictures of CD45 (red) and Keratin 14 (green) staining in skin section of vehicle (left panel) and lorlatinib (right panel). Scale bar = 80 μm (F) Quantification of CD45+ mean fluorescence intensity (n = 5, from one experiment) and (G) Epidermal thickness (based on K14 staining, n = 5, from one experiment). (H) Scratching bouts in mice treated with a single gavage of vehicle or lorlatinib at day 3 (n = 18, from three independent experiments). Values as mean ± SEM, (B) *<0.05, mixed effect model (REML), ##<0.01, Bonferroni's multiple comparison test and (C–D, F–H) ns>0.05, *<0.05, Mann–Whitney t test.
See this image and copyright information in PMC

References

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