Sự biểu hiện của thụ thể IL-17A khác nhau giữa các thể loại của bệnh histiocytosis tế bào Langerhans, có thể giải quyết được vấn đề tranh cãi về IL-17A

Ichiro Murakami1, Akira Morimoto2, Takashi Oka3, Satoshi Kuwamoto1, Masako Kato1, Yasushi Horie4, Kazuhiko Hayashi1, Jean Gogusev5, Francis Jaubert6, Shinsaku Imashuku7, Lamia Abd Al-Kadar3, Katsuyoshi Takata3, Tadashi Yoshino3
1Division of Molecular Pathology, Faculty of Medicine, Tottori University, Yonago, Japan
2Department of Pediatrics, Jichi Medical University School of Medicine, Tochigi, Japan
3Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
4Department of Pathology, Tottori University Hospital, Tottori, Japan
5Inserm U507 and U1016, Institut Cochin, Paris, France
6University of Paris Descartes (Paris V), Paris, France
7Division of Pediatrics and Hematology, Takasago-seibu Hospital, Hyogo, Japan

Tóm tắt

Bệnh histiocytosis tế bào Langerhans (LCH) là một rối loạn lymphoproliferative bao gồm những tế bào bất thường giống như tế bào Langerhans và các tế bào lympho khác. LCH có thể biểu hiện dưới dạng LCH đa hệ (LCH-MS) hoặc LCH đơn hệ (LCH-SS). Hiện tại, cả nguyên nhân bệnh sinh lẫn các yếu tố xác định các tiểu loại bệnh này vẫn chưa được làm rõ. Mô hình tự tiết IL-17A trong LCH và các liệu pháp nhắm mục tiêu IL-17A đã được đưa ra và gây ra nhiều tranh cãi. Các tác giả cho thấy có mức độ IL-17A trong huyết thanh cao ở LCH và lập luận rằng hoạt động hợp nhất phụ thuộc vào IL-17A trong huyết thanh in vitro, thay vì mức độ IL-17A trong huyết thanh, có liên quan đến mức độ nghiêm trọng của LCH (tức là nghịch lý IL-17A). Ngược lại, những người khác không thể xác nhận mô hình tự tiết IL-17A. Và từ đó bắt đầu cuộc tranh cãi về IL-17A, hiện vẫn chưa có hồi kết. Chúng tôi đã tiếp cận cuộc tranh cãi về IL-17A và nghịch lý IL-17A từ một quan điểm mới bằng cách xem xét các mức độ biểu hiện của thụ thể IL-17A (IL-17RA). Chúng tôi phát hiện rằng mức độ biểu hiện protein IL-17RA cao hơn ở LCH-MS (n = 10) so với LCH-SS (n = 9) (P = 0.041) qua phương pháp miễn dịch huỳnh quang. Chúng tôi đã xác nhận lại các dữ liệu này bằng cách phân tích lại dữ liệu mRNA GSE16395. Chúng tôi thấy rằng mức IL-17A trong huyết thanh cao hơn ở LCH (n = 38) so với nhóm chứng (n = 20) (P = 0.005) mà không có sự khác biệt đáng kể giữa các tiểu loại LCH. Chúng tôi đề xuất một mô hình nội tiết IL-17A và nhấn mạnh rằng sự thay đổi trong mức độ biểu hiện IL-17RA là quan trọng để xác định các tiểu loại LCH. Chúng tôi giả thuyết rằng những dữ liệu về IL-17RA này có thể làm sáng tỏ cuộc tranh cãi về IL-17A và nghịch lý IL-17A. Như một phương pháp điều trị tiềm năng cho LCH-MS, chúng tôi chỉ ra khả năng của một liệu pháp nhắm mục tiêu IL-17RA.

Từ khóa


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