γδ T Cell Therapy Development for Psoriasis

Psoriasis is one of the most common skin diseases, characterized by proliferation of keratinocytes, infiltration of T cells, dendritic cells, macrophages and neutrophils. In addition to the traditional T cells, the role of innate immune cells such as γδ T cells in the pathogenesis of psoriasis has attracted more and more attention.

Introduction to Psoriasis

Psoriasis is an immune-mediated chronic disease (a disease of unknown etiology, characterized by inflammation caused by immune system dysfunction). It is characterized by the elevation of abnormal areas of the skin, which can cause skin cells to proliferate 10 times faster than normal. This causes the skin to accumulate into bumpy red patches covering the white scales. They can grow anywhere, but most of them are on the scalp, elbows, knees and lower back. Psoriasis cannot be spread from person to person, and there is no cure.

Fig.1 Dysregulated immune responses in psoriasis. (Cai, 2012)

Role of γδ T Cells in the Development of Psoriasis

At present, a large number of clinical and basic studies show the pathogenic role of interleukin (IL) -17 in the pathogenesis of psoriasis. T helper (Th) 17 cells and their downstream effector molecules including IL-17A, IL-17F, IL-21, IL-22 and tumor necrosis factor (TNF-α) were elevated in humans psoriatic lesions and circulation. Psoriasis is a typical inflammatory disease driven by organ specific T cells. In the past few years, it has been proved that the γδ T cells that produce IL-17 play an important role in some infectious and autoimmune diseases. After being stimulated by IL-23 and IL-1β or danger signals, they are activated rapidly, and then they initially act as astrocytes and enhance Th17 cell-mediated immune response.

Fig.2 Development of dermal γδ T cells and their roles in psoriasis immunopathogenesis. (Cai, 2013)

Application of γδ T Cell Therapy in Psoriasis

In recent years, as the important role of dermal γδ T cells in the pathogenesis of psoriasis has been revealed, dermal γδ T cells and related molecules are becoming potential candidate cells for the treatment of psoriasis. So far, there are several monoclonal antibodies targeting IL-23p40, IL-17 or IL-17R in clinical studies, which have shown significant efficacy in the treatment of moderate to severe psoriasis. However, blocking the upstream cytokine IL-23 can cause nonspecific biological effects. In this case, targeting IL-17 or IL-17R may be a better long-term safety option. CCR6 was constitutively expressed in dermal γδ T cells. CCR6 KO mice were resistant to IL-23-induced skin inflammation. At the same time, anti-CCL20 monoclonal antibody treatment also showed a reduction of psoriasis-like dermatitis in mice, suggesting that CCR6 or its ligand CCL20 may be a potential target for the treatment of psoriasis.

What Can We Do?

As mentioned above, the new T cell subsets involved in the pathogenesis of psoriasis, γδ T cells, may be candidates for immunotherapy of psoriasis in the future. In addition to some existing target studies, we hope to expand the understanding of T cells involved in the development of diseases, and to find more specific targets for future drug therapy.

Based on our rich experience in the field of immunotherapy, Creative Biolabs has actively seized this opportunity and launched several services based on the research of γδ T cell therapy, including γδ T Cell Development Services, γδ T Cell Receptors Services, γδ T Cell Engineering Services, to provide considerate and high-quality services for our researchers from all over the world. If you are interested in our service, please contact us.

References

1. Cai, Y., et al. New insights of T cells in the pathogenesis of psoriasis. Cellular & molecular immunology. 2012, 9(4): 302-309.
2. Cai, Y., et al. Dermal γδ T cells - A new player in the pathogenesis of psoriasis. International Immunopharmacology. 2013, 16(3): 388-391.