The Journal of allergy and clinical immunology · 2024
Single-cell sequencing delineates T-cell clonality and pathogenesis of the parapsoriasis disease group.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Alkon Natalia, Chennareddy Sumanth, Cohenour Emry R, Ruggiero John R, Stingl Georg, Bangert Christine, Rindler Katharina, Bauer Wolfgang M, Weninger Wolfgang, Griss Johannes, Jonak Constanze, Brunner Patrick M
Аннотация
BACKGROUND: Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is often underdiagnosed in early stages because of similarities with benign dermatoses such as atopic dermatitis (AD). Furthermore, the delineation from what is called "parapsoriasis en plaque", a disease that can appear either in a small- or large-plaque form, is still controversial.
OBJECTIVE: We sought to characterize the parapsoriasis disease spectrum.
METHODS: We performed single-cell RNA sequencing of skin biopsies from patients within the parapsoriasis-to-early-stage MF spectrum, stratified for small and large plaques, and compared them to AD, psoriasis, and healthy control skin.
RESULTS: Six of 8 large-plaque lesions harbored either an expanded alpha/beta or gamma/delta T-cell clone with downregulation of CD7 expression, consistent with a diagnosis of early-stage MF. In contrast, 6 of 7 small-plaque lesions were polyclonal in nature, thereby lacking a lymphomatous phenotype, and also revealed a less inflammatory microenvironment than early-stage MF or AD. Of note, polyclonal small- and large-plaque lesions characteristically harbored a population of NPY+ innate lymphoid cells and displayed a stromal signature of complement upregulation and antimicrobial hyperresponsiveness in fibroblasts and sweat gland cells, respectively. These conditions were clearly distinct from AD or psoriasis, which uniquely harbored CD3+CRTH2+ IL-13 expressing "TH2A" cells, or strong type 17 inflammation, respectively.
CONCLUSION: These data position polyclonal small- and large-plaque parapsoriasis lesions as a separate disease entity that characteristically harbors a so far undescribed innate lymphoid cell population. We thus propose a new term, "polyclonal parapsoriasis en plaque", for this kind of lesion because they can be clearly differentiated from early- and advanced-stage MF, psoriasis, and AD on several cellular and molecular levels.
OBJECTIVE: We sought to characterize the parapsoriasis disease spectrum.
METHODS: We performed single-cell RNA sequencing of skin biopsies from patients within the parapsoriasis-to-early-stage MF spectrum, stratified for small and large plaques, and compared them to AD, psoriasis, and healthy control skin.
RESULTS: Six of 8 large-plaque lesions harbored either an expanded alpha/beta or gamma/delta T-cell clone with downregulation of CD7 expression, consistent with a diagnosis of early-stage MF. In contrast, 6 of 7 small-plaque lesions were polyclonal in nature, thereby lacking a lymphomatous phenotype, and also revealed a less inflammatory microenvironment than early-stage MF or AD. Of note, polyclonal small- and large-plaque lesions characteristically harbored a population of NPY+ innate lymphoid cells and displayed a stromal signature of complement upregulation and antimicrobial hyperresponsiveness in fibroblasts and sweat gland cells, respectively. These conditions were clearly distinct from AD or psoriasis, which uniquely harbored CD3+CRTH2+ IL-13 expressing "TH2A" cells, or strong type 17 inflammation, respectively.
CONCLUSION: These data position polyclonal small- and large-plaque parapsoriasis lesions as a separate disease entity that characteristically harbors a so far undescribed innate lymphoid cell population. We thus propose a new term, "polyclonal parapsoriasis en plaque", for this kind of lesion because they can be clearly differentiated from early- and advanced-stage MF, psoriasis, and AD on several cellular and molecular levels.