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Tolerogenic Dendritic Cell – Function & Significance

Tolerogenic dendritic cells are specialised immune cells that suppress excessive immune responses and promote immunological tolerance throughout the body.

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Things worth knowing about "Tolerogenic dendritic cell"

Tolerogenic dendritic cells are specialised immune cells that suppress excessive immune responses and promote immunological tolerance throughout the body.

What are tolerogenic dendritic cells?

Tolerogenic dendritic cells (tDCs) are a functionally specialised subset of dendritic cells, which belong to the antigen-presenting cells of the immune system. While classical, immunogenic dendritic cells activate T lymphocytes and trigger an immune response, tolerogenic dendritic cells fulfil the opposite role: they promote immunological tolerance – the ability of the immune system to refrain from attacking harmless or self-derived structures.

These cells occur naturally throughout the body – in lymph nodes, the spleen, mucosal tissues, and the blood – and play a central role in preventing autoimmune diseases, controlling allergies, and maintaining tolerance towards the foetus during pregnancy.

Mechanism of action

Tolerogenic dendritic cells differ from immunogenic dendritic cells in several key functional features:

Low expression of co-stimulatory molecules: tDCs present antigens without providing sufficient co-stimulatory signals (e.g. CD80, CD86), leading to T-cell anergy (inactivation) rather than activation.
Promotion of regulatory T cells (Tregs): tDCs induce the differentiation of naive T cells into regulatory T cells (Tregs), which actively suppress pro-inflammatory immune responses.
Production of anti-inflammatory mediators: tDCs secrete cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), which inhibit inflammatory processes.
Induction of T-cell apoptosis: Through the expression of molecules such as FasL, tDCs can direct reactive T cells into programmed cell death.
Increased IDO activity: The enzyme indoleamine 2,3-dioxygenase (IDO) degrades tryptophan, creating a microenvironment that is unfavourable for T-cell survival.

Clinical relevance

Autoimmune diseases

In conditions such as multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, the tolerogenic function of dendritic cells is impaired. The immune system mistakenly recognises self-structures as foreign and attacks them. tDCs therefore represent a promising therapeutic target for correcting this dysregulation.

Transplantation medicine

In organ transplantation, preventing rejection reactions is a central challenge. Tolerogenic dendritic cells could help induce donor-specific tolerance and thereby reduce the need for lifelong immunosuppression.

Allergies and asthma

tDCs also play a role in allergic diseases. They can dampen excessive immune responses to harmless substances such as pollen or food allergens and are being studied in the context of allergen immunotherapy.

Pregnancy

During pregnancy, tDCs prevent the maternal immune system from rejecting the semi-foreign foetus. They make a key contribution to foetal tolerance.

Therapeutic approaches

The targeted use of tolerogenic dendritic cells as a therapy is being intensively researched. Dendritic cells are isolated from a patient's blood, conditioned in the laboratory to a tolerogenic phenotype, and then reintroduced into the body. Conditioning strategies include:

Treatment with vitamin D3 or its analogues
Exposure to IL-10 or TGF-β
Use of mTOR inhibitors (e.g. rapamycin)
Genetic modification to overexpress tolerogenic factors

Early clinical trials have shown promising results in patients with rheumatoid arthritis, type 1 diabetes, and following kidney transplantation. However, the technology is still largely in early clinical phases.

References

Steinman, R. M., Hawiger, D. & Nussenzweig, M. C. (2003). Tolerogenic dendritic cells. Annual Review of Immunology, 21, 685–711.
Hilkens, C. M. U. et al. (2010). Tolerogenic dendritic cell therapy for rheumatoid arthritis: where are we now? Clinical and Experimental Immunology, 161(1), 10–19.
Thomson, A. W. & Metes, D. (2021). Tolerogenic dendritic cells in clinical use. Transplantation, 105(3), 501–511.

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