γδ T Cell Therapy Development for Idiopathic Bowel Diseases (IBD)

Brief Introduction to Idiopathic Bowel Diseases

The human gastrointestinal tract is performing a diversity of immune responses since it is always indirectly exposed to various antigens found in food and microbiota. Under normal conditions, the body maintains intestinal homeostasis by inhibiting the excessive immune response to these antigens. Once the homeostasis is disturbed, it can cause intestinal inflammation. Idiopathic bowel disease (IBD), also known as inflammatory bowel disease, will be caused by this chronic and prolonged, or excessive inflammation in the gastrointestinal tract.

IBD is mainly caused by intestinal inflammation resulted from mucosal immunity or abnormal autoimmunity. Numbers of studies have revealed that excessive secretion of cytokines (mainly interleukin-17 (IL17)) and over-active T lymphocytes play an important role in the pathogenesis and progression of IBD, including both two clinical phenomena Crohn's disease (CD) and ulcerative colitis (UC).

Fig.1 Pathogenesis of inflammatory bowel disease. (Biasi, 2011)

γδ T Cell Functions in Idiopathic Bowel Disease

The human γδ T cell is a small group of T lymphocytes characterized by the γδ T-cell receptor (TCR). Γδ TCR on the surface of γδ T cell is a heterodimer that composed of two chains: γ chain and δ chain. γδ T cell can be roughly defined as Vδ1 T cells, Vδ2 T cells, and other γδ T subgroups according to the expressed δ chain type of TCR. Among these γδ T cells, Vδ1 T cell is a relatively rare subset that resides mainly in skin, epidermis, intestinal epithelium, and other mucosal tissues, which is an essential component of intraepidermal lymphocytes (IEL) and play an important role in mucosal immunity and inflammations.

• Large evidence indicated that γδ T cell has a protective role against CD.
  1. γδ T cells, mostly Vδ1 T cells, quickly responded to intestinal antigens and infections, and regulated both the innate and adaptive immune responses.
  2. γδ T cells can promote the maturation of dendritic cells and activate neutrophils, B cells, and macrophages to kill infected cells.
  3. Mucosal γδ T cells facilitate epithelial regeneration and wound healing by producing multiple growth factors.
  4. γδ T cells secret immunosuppressant cytokines, such as transforming growth factor-β (TGF-β) or IL-10, to prevent an excessive immune response.
• However, it also has been reported that γδ T cells exhibited a pro-inflammatory effect on transgenic colitis models and IBD. Higher activated γδ T cells, mostly Vδ2 T cells, and pro-inflammatory cytokines (such as IL-17 and TGF-α) could be observed in the intestinal mucosa of CD patients. Approaches for IBD immunotherapy using γδ T cells are still being explored.

Fig.2 Immunoregulatory functions of γδ T cells in CD. (Papotto, 2018)

γδ T Cell Therapy Development Services at Creative Biolabs

It has been concluded that γδ T cells have both protective and pathogenic effects on IBD. Potential γδ T cell therapy for the treatment of IBD still needs to be fully and deeply researched and explored. Creative Biolabs is an innovative biotech company that has won a good reputation in the field of immunotherapy. We are happy to offer tailored solutions and services for the IBD immunotherapy development by γδ T cell or modified γδ T cell.

If you are interested in or have any questions, just directly contact us, our seasoned scientists will offer you the most detailed solutions and support.

References

1. Biasi, F., et al. Polyphenol Supplementation as a Complementary Medicinal Approach to Treating Inflammatory Bowel Disease. Current Medicinal Chemistry. 2011, 18: 4851-4865.
2. Catalan-Serra, I., et al. Gammadelta T cells in Crohn’s disease: a new player in the disease pathogenesis? Journal of Crohn's and Colitis. 2017, 11(9): 1135-1145.