| Autor: |
Claire, Barbieux, Mathilde, Bonnet des Claustres, Matthias, Fahrner, Evgeniya, Petrova, Lam C, Tsoi, Olivier, Gouin, Florent, Leturcq, Pascale, Nicaise-Roland, Christine, Bole, Vivien, Béziat, Emmanuelle, Bourrat, Oliver, Schilling, Johann E, Gudjonsson, Alain, Hovnanian |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
The Journal of allergy and clinical immunology. 149(4) |
| ISSN: |
1097-6825 |
| Popis: |
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).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.We studied a cohort of 13 patients comprising 9 NS-ILC and 4 NS-SE.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 TThis 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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