Preparation of Tolerogenic DCs for Autoimmune Diseases Therapy

To avoid the outbreak of autoimmune diseases or chronic inflammation, autoreactive T cells that are not deleted in the thymus need to be controlled in the periphery by several mechanisms, collectively described as peripheral tolerance where tolerogenic dendritic cells (tDCs) participate actively. Tolerogenic dendritic cells play important roles in autoimmune diseases and thus show a potential strategy to deal with autoimmune diseases. Equipped with advanced facilities, the latest technologies, and experienced specialists, Creative Biolabs is confident in offering reliable tolerogenic DCs preparation services to global customers.

Introduction of Tolerogenic Dendritic Cells

Dendritic cells (DCs) are a heterogeneous group of professional antigen-presenting cells (APC) involved in the initiation of both immunity and tolerance induction. tDCs avoid the activation of autoreactive T cells by inducing apoptosis, skewing phenotype, anergy, and/or regulatory T cells (Tregs). Therefore, in genetically susceptible individuals, autoimmune diseases may develop as a result of direct alterations in several stages of the tolerogenic DC functions, such as differentiation, migration, maturation/activation, antigen presentation, cytokines secretion, genetic expression, etc. In addition, indirect alterations mediated by DC such as changes in the expression of self-antigens, release of hidden antigens, and access to immunologically privileged sites have been also associated with the pathophysiology of autoimmune diseases.

The balance between tolerogenic and immunogenic function of DCs may be shifted by external factors and induce autoimmune diseases. Fig.1 The balance between tolerogenic and immunogenic function of DCs may be shifted by external factors and induce autoimmune diseases. (Torres-Aguilar, 2010)

Strategies to Generate Tolerogenic Dendritic Cells

Due to DCs' plasticity to respond to external factors, a number of immunomodulatory agents modifying the phenotype, cytokine profiles, stimulatory ability, and several DCs functions have been tested. These agents included dexamethasone, 1α,25-dihydroxy vitamin D3, salicylates, mycophenolate, IL-10 TGF-β, TNF-α, macrophages colony stimulator factor (M-CSF), hepatocytes growth factor (HGF), IL-21, thymic stromal lymphopoietin (TSLP), vasoactive intestinal peptide (VIP), intravenous immunoglobulin (IVIg), among much others. In general, these alternatively activated DCs (aaDCs) show characteristics of semimature DCs, maintain increased expression of monocyte/macrophages and endocytic markers.

It has been demonstrated that human monocyte-derived DCs treated with IL-10 and TGF-β1 (10/TGF-DC) are able to induce tetanus toxoid-specific tolerance and Tregs cells in memory T cells of healthy volunteers vaccinated with tetanus toxoid. In addition, researches showed that 10/TGF-DC induces in vitro insulin and β2GPI-specific tolerance in effector/memory T cells derived from type 1 diabetes and antiphospholipid syndrome patients respectively. This tolerance induction has depended on the current activation state of CD4+ T cells in each patient, indicating that the application of tDC in clinical assays would require a bespoke therapy depending on an initial analysis of the activation state of CD4+ T cells, in order to improve the efficiency of tDC-based therapies.

Several external factors induce tolerogenic functions in dendritic cells. Fig.2 Several external factors induce tolerogenic functions in dendritic cells. (Torres-Aguilar, 2010)

Custom Services of Tolerogenic DCs Preparation for Autoimmune Diseases Therapy

Focusing on dendritic cell-based therapy for years, Creative Biolabs has accumulated extensive experience from practice step-by-step. To provide our customers with the best services, we have equipped our platform with advanced experimental foundations, the latest technologies, and Ph.D. level experts. Every effort we make is to let customers enjoy more comfortable services.

  • Top-rated customer experience
  • Hundreds of successful precedents
  • Professional expert team with advanced degrees
  • Efficient and cost-effective

With advantages in multiple aspects, Creative Biolabs is confident in providing global customers with high-quality tDCs preparation services. We are eager to promote the development of therapeutic strategies for autoimmune diseases through our reliable services. If you are interested in the preparation of tDCs or you have any questions about our relevant services, please don't hesitate to contact us for more information.

Reference

  1. Torres-Aguilar, H.; et al. Tolerogenic dendritic cells in autoimmune diseases: Crucial players in induction and prevention of autoimmunity. Autoimmun Rev. 2010, 10(1): 8-17.

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