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The RELT Family of Proteins: An Increasing Awareness of Their Importance for Cancer, the Immune System, and
John K Cusick1, Jessa Alcaide1, Yihui Shi1,2
1College of Medicine, California Northstate University, Elk Grove, CA 95757, USA.
Abstract:
This review highlights Receptor Expressed in Lymphoid Tissues (RELT), a Tumor Necrosis Factor Superfamily member, and its two paralogs, RELL1 and RELL2. Collectively, these three proteins are referred to as RELTfms and have gained much interest in recent years due to their association with cancer and other human diseases. A thorough knowledge of their physiological functions, including the ligand for RELT, is lacking, yet emerging evidence implicates RELTfms in a variety of processes including cytokine signaling and pathways that either promote cell death or survival. T cells from mice lacking RELT exhibit increased responses against tumors and increased inflammatory cytokine production, and multiple lines of evidence indicate that RELT may promote an immunosuppressive environment for tumors. The relationship of individual RELTfms in different cancers is not universal however, as evidence indicates that individual RELTfms may be risk factors in certain cancers yet appear to be protective in other cancers. RELTfms are important for a variety of additional processes related to human health including microbial pathogenesis, inflammation, behavior, reproduction, and development. All three proteins have been strongly conserved in all vertebrates, and this review aims to provide a clearer understanding of the current knowledge regarding these interesting proteins.
Insights
Receptor Expressed in Lymphoid Tissues family members (RELTfms) are implicated in cancer and disease. While their exact roles are still being uncovered, they influence immune responses and cell survival pathways, impacting various human health processes.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Receptor Expressed in Lymphoid Tissues (RELT) is a member of the Tumor Necrosis Factor Superfamily.
- RELT has two paralogs: RELL1 and RELL2. Collectively, these are known as RELTfms.
- RELTfms are increasingly recognized for their association with cancer and other human diseases.
Purpose of the Study:
- To review current knowledge on the physiological functions of RELTfms.
- To explore the emerging roles of RELTfms in cytokine signaling, cell death, and survival pathways.
- To clarify the complex and sometimes contradictory roles of RELTfms in various cancer types.
Main Methods:
- Literature review of existing studies on RELTfms.
- Analysis of evidence regarding immune responses in RELT-deficient models.
- Examination of data on the involvement of RELTfms in human diseases and physiological processes.
Main Results:
- RELTfms are involved in processes regulating cell death and survival.
- RELT-deficient T cells show enhanced anti-tumor responses and increased inflammatory cytokine production.
- RELTfms exhibit context-dependent roles in cancer, acting as risk factors or protective elements.
- RELTfms are conserved across vertebrates and play roles in microbial pathogenesis, inflammation, reproduction, and development.
Conclusions:
- RELTfms are crucial regulators of immune responses and cellular fate.
- Further research is needed to fully elucidate the ligand for RELT and the precise mechanisms of RELTfm action.
- Understanding RELTfms offers potential for novel therapeutic strategies in cancer and other diseases.
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