2019
DOI: 10.1111/bjd.18264
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Apremilast and tofacitinib exert differential effects in the humanized mouse model of alopecia areata

Abstract: skin diseases reflected in the Cochrane Database of Systematic Reviews, 5 where psoriasis and decubitus ulcer were overrepresented diseases in terms of research, whereas urticaria and bacterial skin infections were underrepresented. A strength of this study is the interrelationship made between two large national datasets, from studies designed to be representative both of outpatient consultations and research activity in Spain, 3,4 and data from the GBDS. Among the limitations are that this study is restricte… Show more

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Cited by 5 publications
(8 citation statements)
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“…Based on our long‐standing experience with humanized mouse models for psoriasis 128 and alopecia areata, 131 we expect that the systematic exploration of split thickness human skin xenotransplants on SCID mice likewise offers a particularly promising strategy for meeting the majority of the criteria identified above. If lesional AD skin is transplanted ideally to fully humanized SCID mice, the in vivo response of human AD to topical or systemic candidate therapeutics can likely be studied with much greater predictive value for clinical outcomes than any of the currently available mouse models.…”
Section: Conclusion and Future Perspectivesmentioning
confidence: 99%
See 1 more Smart Citation
“…Based on our long‐standing experience with humanized mouse models for psoriasis 128 and alopecia areata, 131 we expect that the systematic exploration of split thickness human skin xenotransplants on SCID mice likewise offers a particularly promising strategy for meeting the majority of the criteria identified above. If lesional AD skin is transplanted ideally to fully humanized SCID mice, the in vivo response of human AD to topical or systemic candidate therapeutics can likely be studied with much greater predictive value for clinical outcomes than any of the currently available mouse models.…”
Section: Conclusion and Future Perspectivesmentioning
confidence: 99%
“…We have shown that the intradermal injection of autologous PBMCs that have been pretreated in vitro with appropriate cytokine stimuli can robustly induce skin lesions in previously healthy human skin that are macroscopically and histologically indistinguishable from psoriasis 128 or alopecia areata lesions 131 . Therefore, it is reasonable to assume that the same can be achieved for AD lesions if one identifies and employs the right combination of AD‐promoting stimuli.…”
Section: Conclusion and Future Perspectivesmentioning
confidence: 99%
“…[134][135][136] The question of whether IL-23 antagonism, such as through ustekinumab therapy, can reproducibly promote hair regrowth in patients with AA awaits systemic analysis. 137 Only a mild therapeutic effect was observed after treatment with IL-17, 138 whereas the phosphodiesterase 4 antagonist apremilast had insufficient therapeutic effects in patients with AA 139 and in the humanized AA mouse model, 140 in which apremilast nevertheless inhibited experimental induction of AA lesions in vivo. Collectively, in addition to targeting IFN-g-and JAK/ STAT-mediated signaling in patients with AA, several additional pathways that also deserve therapeutic targeting, at least in selected AA subpopulations/subtypes, deserve systematic exploration.…”
Section: Novel Therapeutic Intervention Strategiesmentioning
confidence: 99%
“…This immune phenotype suggests that the immune cells used in our study are best classified as ILC1-like cells (Nabekura et al, 2021a), and documents that all experiments reported below were indeed performed with autologous ILC1-like cells rather than with NK cell subpopulations. Note that we had previously shown that NKG2D+/CD56+ NK cells suffice to induce AA lesions in human skin in vivo (Gilhar et al, 2013a;Laufer Britva et al, 2020) while iNKT cells are AA-protective in the humanized AA mouse model (Ghraieb et al, 2018). Subsequently, these ILC1-like cells were either used for HF co-culture assays or injected into healthy human scalp skin xenotransplants on SCID/beige mice (Gilhar et al, 2013a;Ito et al, 2005a).…”
Section: T-bet Lo /Eomes Hi Ilc1-like Cells Can Be Expanded From Huma...mentioning
confidence: 99%
“…Hematoxylin and eosin (H&E) staining was performed on cryo-or paraffin sections as previously described (Keren et al, 2018). For the ex vivo experiments, HFs cryosections were dehydrated for 40 minutes and fixed with acetone for 10 minutes at -20 o C (Ghraieb et al, 2018;Laufer Britva et al, 2020;Keren et al, 2015). The following primary antibodies were used for immunohistochemistry (IHC) or immunofluorescence microscopy (IF) of key HF immune privilege markers (Bertolini et al, 2020;Paus et al, 2005) The immunoreactivity patterns were assessed in standardized, well-defined reference areas by quantitative immunohistomorphoemtry (qIHM) by experienced, blinded observers, following our standard protocols for evaluating human HF immunology read-outs (Bertolini et al, 2014;Bertolini et al, 2016;Christoph et al, 2000;Harries et al, 2013b;Hardman-Smart et al, 2020), counting at least three reference areas each on three non-consecutive sections, presented randomly to the blinded observer(s).…”
Section: Histochemistry Immunohistology and Quantitative Immunohistom...mentioning
confidence: 99%