Tnfrsf10b, also known as TRAIL-R2 or DR5, codes for a pro-apoptotic receptor activated by TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand), which belongs to the TNF superfamily. It is involved in the apoptosis pathway, playing a crucial role in regulating cell death, and has significance in immune surveillance against virus-infected or transformed cells [1,2,3].

In chronic lymphocytic leukemia (CLL), loss of one copy of the Tnfrsf10b gene due to del(8p) is associated with a poor prognosis, shorter time to first treatment, worse overall survival, and resistance to fludarabine-based regimens. Tnfrsf10b was haploinsufficient in del(8p) CLL, and experiments in primary cells and CRISPR-edited Tnfrsf10b knockout CLL cell lines confirmed its involvement in modulating fludarabine-induced cell death [1]. In diabetic kidney disease, single cell RNA sequencing data showed increased Tnfrsf10b expression in podocytes of patients with DKD. Podocyte-specific deletion of Tnfrsf10b in obese diabetic mice alleviated podocyte and glomerular injury, associated with decreased podocyte PANoptosis [2].

In conclusion, Tnfrsf10b is essential for apoptosis regulation. Gene knockout models have revealed its role in diseases like CLL and diabetic kidney disease, highlighting its importance in understanding disease mechanisms and potentially developing targeted therapies for these conditions.

References:

1. Jondreville, Ludovic, Dehgane, Lea, Doualle, Cecile, Susin, Santos A, Nguyen-Khac, Florence. 2023. del(8p) and TNFRSF10B loss are associated with a poor prognosis and resistance to fludarabine in chronic lymphocytic leukemia. In Leukemia, 37, 2221-2230. doi:10.1038/s41375-023-02035-3. https://pubmed.ncbi.nlm.nih.gov/37752286/

2. Lv, Zhimei, Hu, Jinxiu, Su, Hong, Shen, Ning, Wang, Rong. 2024. TRAIL induces podocyte PANoptosis via death receptor 5 in diabetic kidney disease. In Kidney international, 107, 317-331. doi:10.1016/j.kint.2024.10.026. https://pubmed.ncbi.nlm.nih.gov/39571905/

3. Shin, Gu-Choul, Kang, Hong Seok, Lee, Ah Ram, Kim, Kyun-Hwan. 2016. Hepatitis B virus-triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response. In Autophagy, 12, 2451-2466. doi:. https://pubmed.ncbi.nlm.nih.gov/27740879/