Tolerogenic dendritic cells for reprogramming of lymphocyte responses in autoimmune diseases

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• 作者：Paulina Garcí ; a-Gonzá ; lez ; Gabriela Ubilla-Olguí ; n ; Diego Catalá ; n ; Katina Schinnerling ; ^{katina.schinnerling@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Juan Carlos Aguilló ; n ; ^{jaguillo@med.uchile.cl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DCs ; Dendritic cells ; tolDcs ; Tolerogenic dendritic cells ; IL ; Interleukin ; APCs ; Antigen presenting cells ; TCR ; T cell antigen receptor ; MHC ; Major histocompatibility complex ; TLR ; Toll-like receptor ; RA ; Rheumatoid arthritis ; TNF-α ; Tumor necrosis factor-α ; iNOS ; Inducible nitric oxide synthase ; IFN-α ; Interferon-α ; HLA ; Human leukocyte antigen ; TGF-β ; Transforming growth factor β ; IDO ; Indoleamine 2 ; 3-dioxygenase ; Treg ; Regulatory T cells ; T1D ; Type 1 diabetes mellitus ; SLE ; Systemic lupus er
• 刊名：Autoimmunity Reviews
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：15
• 期：11
• 页码：1071-1080
• 全文大小：473 K

文摘

Dendritic cells (DCs) control immune responses by driving potent inflammatory actions against external and internal threats while generating tolerance to self and harmless components. This duality and their potential to reprogram immune responses in an antigen-specific fashion have made them an interesting target for immunotherapeutic strategies to control autoimmune diseases. Several protocols have been described for in vitro generation of tolerogenic DCs (tolDCs) capable of modulating adaptive immune responses and restoring tolerance through different mechanisms that involve anergy, generation of regulatory lymphocyte populations, or deletion of potentially harmful inflammatory T cell subsets. Recently, the capacity of tolDCs to induce interleukin (IL-10)-secreting regulatory B cells has been demonstrated. In vitro assays and rodent models of autoimmune diseases provide insights to the molecular regulators and pathways enabling tolDCs to control immune responses. Here we review mechanisms through which tolDCs modulate adaptive immune responses, particularly focusing on their suitability for reprogramming autoreactive CD4⁺ effector T cells. Furthermore, we discuss recent findings establishing that tolDCs also modulate B cell populations and discuss clinical trials applying tolDCs to patients with autoimmune diseases.