Netherton syndrome subtypes share IL-17/IL-36 signature with distinct IFN-[alpha] and allergic responses : = Netherton syndrome subtypes share IL-17/IL-36 signature with distinct IFN-α and allergic responses

Abstract: Background

Netherton syndrome (NS) is a rare recessive skin disorder caused by loss-of-function mutations in SPINK5 encoding the protease inhibitor LEKTI (lymphoepithelial Kazal-type–related inhibitor). NS patients experience severe skin barrier defects, display inflammatory skin lesions, and have superficial scaling with atopic manifestations. They present with typical ichthyosis linearis circumflexa (NS-ILC) or scaly erythroderma (NS-SE).
Objective

We used a combination of several molecular profiling methods to comprehensively characterize the skin, immune cells, and allergic phenotypes of NS-ILC and NS-SE patients.
Methods

We studied a cohort of 13 patients comprising 9 NS-ILC and 4 NS-SE.
Results

Integrated multiomics revealed abnormal epidermal proliferation and differentiation and IL-17/IL-36 signatures in lesion skin and in blood in both NS endotypes. Although the molecular profiles of NS-ILC and NS-SE lesion skin were very similar, nonlesion skin of each disease subtype displayed distinctive molecular features. Nonlesion and lesion NS-SE epidermis showed activation of the type I IFN signaling pathway, while lesion NS-ILC skin differed from nonlesion NS-ILC skin by increased complement activation and neutrophil infiltration. Serum cytokine profiling and immunophenotyping of circulating lymphocytes showed a TH2-driven allergic response in NS-ILC, whereas NS-SE patients displayed mainly a TH9 axis with increased CCL22/MDC and CCL17/TARC serum levels.
Conclusions

This study confirms IL-17/IL-36 as the predominant signaling axes in both NS endotypes and unveils molecular features distinguishing NS-ILC and NS-SE. These results identify new therapeutic targets and could pave the way for precision medicine of NS

Angaben zum Objekt

• Weitere Titel: Netherton syndrome subtypes share IL-17/IL-36 signature with distinct IFN-α and allergic responses
• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: The journal of allergy and clinical immunology. - 149, 4 (2022) , 1358-1372, ISSN: 1097-6825

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: Barbieux, Claire ; Claustres, Mathilde Bonnet des ; Fahrner, Matthias ; Petrova, Evgeniya ; Tsoi, Lam C. ; Gouin, Olivier ; Leturcq, Florent ; Nicaise-Roland, Pascale ; Bole, Christine ; Béziat, Vivien ; Bourrat, Emmanuelle ; Schilling, Oliver ; Gudjonsson, Johann E. ; Hovnanian, Alain

Weitere Informationen

• DOI: 10.1016/j.jaci.2021.08.024
• URN: urn:nbn:de:bsz:25-freidok-2214702
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:38 MESZ