Các tế bào gốc trung mô người điều chế phản ứng của tế bào miễn dịch đồng loại
Tóm tắt
Các tế bào gốc trung mô (MSCs) là các tế bào đa năng được tìm thấy trong một số mô trưởng thành. Các MSCs đồng loại được cấy ghép có thể được phát hiện trong những người nhận tại các thời điểm lâu dài, cho thấy sự thiếu nhận diện và thanh thải miễn dịch. Ngoài ra, một vai trò của các MSCs thu được từ tủy xương trong việc giảm tần suất và mức độ nghiêm trọng của bệnh ghép chống chủ (GVHD) trong quá trình cấy ghép đồng loại gần đây đã được báo cáo; tuy nhiên, các cơ chế vẫn cần được điều tra. Chúng tôi đã nghiên cứu các chức năng điều biến miễn dịch của hMSCs (các tế bào gốc trung mô người) bằng cách đồng nuôi chúng với các phân nhóm tế bào miễn dịch tinh khiết và báo cáo ở đây rằng hMSCs đã thay đổi hồ sơ tiết cytokine của các tế bào biểu bì (DCs), tế bào T chưa trưởng thành và tế bào T hiệu ứng (tế bào T hỗ trợ 1 [TH1] và TH2), và các tế bào giết tự nhiên (NK) để tạo ra kiểu hình chống viêm hoặc miễn dịch dung nạp hơn. Cụ thể, hMSCs đã làm giảm sự tiết yếu tố hoại tử khối u α (TNF-α) của các DC trưởng thành loại 1 (DC1) và làm tăng sự tiết interleukin-10 (IL-10) của các DC trưởng thành loại 2 (DC2); hMSCs đã làm giảm mức interferon γ (IFN-γ) của các tế bào TH1 và làm tăng sự tiết IL-4 của các tế bào TH2; hMSCs đã làm tăng tỷ lệ tế bào T điều hòa (TRegs) hiện diện; và hMSCs đã làm giảm sự tiết IFN-γ từ các tế bào NK. Về mặt cơ chế, hMSCs sản xuất mức prostaglandin E2 (PGE2) cao trong các nuôi cấy đồng, và các chất ức chế sản xuất PGE2 đã làm giảm điều biến miễn dịch do hMSCs trung gian. Dữ liệu này cung cấp cái nhìn sâu sắc về các tương tác giữa MSCs đồng loại và các tế bào miễn dịch và cung cấp các cơ chế có khả năng liên quan tới sự phát động dung nạp do MSCs trung gian in vivo có thể có tác dụng điều trị cho việc giảm GVHD, sự từ chối và điều biến viêm. (Blood. 2005;105:1815-1822)
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Tài liệu tham khảo
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