Related Experiment Video
Updated: Aug 5, 2025
Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77
Published on: August 17, 2015
The NLR gene family: from discovery to present day
Wei-Chun Chou1,2, Sushmita Jha3, Michael W Linhoff4,5
1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Abstract:
The mammalian NLR gene family was first reported over 20 years ago, although several genes that were later grouped into the family were already known at that time. Although it is widely known that NLRs include inflammasome receptors and/or sensors that promote the maturation of caspase 1, IL-1β, IL-18 and gasdermin D to drive inflammation and cell death, the other functions of NLR family members are less well appreciated by the scientific community. Examples include MHC class II transactivator (CIITA), a master transcriptional activator of MHC class II genes, which was the first mammalian NBD-LRR-containing protein to be identified, and NLRC5, which regulates the expression of MHC class I genes. Other NLRs govern key inflammatory signalling pathways or interferon responses, and several NLR family members serve as negative regulators of innate immune responses. Multiple NLRs regulate the balance of cell death, cell survival, autophagy, mitophagy and even cellular metabolism. Perhaps the least discussed group of NLRs are those with functions in the mammalian reproductive system. The focus of this Review is to provide a synopsis of the NLR family, including both the intensively studied and the underappreciated members. We focus on the function, structure and disease relevance of NLRs and highlight issues that have received less attention in the NLR field. We hope this may serve as an impetus for future research on the conventional and non-conventional roles of NLRs within and beyond the immune system.
Insights
The NLR gene family, known for inflammasomes, has diverse roles beyond immunity. This review explores underappreciated functions in cellular processes and reproduction, urging further research.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- The NLR gene family, identified over 20 years ago, includes inflammasome sensors crucial for inflammation and cell death.
- While inflammasome roles are recognized, other NLR functions are less understood by the scientific community.
Purpose of the Study:
- To provide a comprehensive overview of the NLR gene family, encompassing both well-studied and underappreciated members.
- To highlight the diverse functions, structure, and disease relevance of NLR proteins.
- To stimulate further research into the conventional and non-conventional roles of NLRs.
Main Methods:
- Literature review and synthesis of existing research on NLR family members.
- Analysis of published data on NLR structure, function, and disease associations.
- Identification of research gaps and under-explored areas within the NLR field.
Main Results:
- NLRs are involved in crucial cellular processes including MHC gene regulation (e.g., CIITA, NLRC5), inflammatory signaling, and interferon responses.
- Several NLRs act as negative regulators of innate immunity and modulate cell death, survival, autophagy, mitophagy, and metabolism.
- A significant, under-explored area of NLR function lies within the mammalian reproductive system.
Conclusions:
- The NLR gene family possesses a broader range of functions than commonly appreciated, extending beyond inflammasome-mediated immunity.
- Further investigation into the diverse roles of NLRs, particularly in reproduction and non-immune pathways, is warranted.
- Understanding the full spectrum of NLR functions is critical for advancing knowledge in immunology, cell biology, and disease pathogenesis.
Related Concept Videos
00:43Bacterial RNA Polymerase
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
01:53Bacterial Transcription
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
02:39lncRNA - Long Non-coding RNAs
03:21Genome Size and the Evolution of New Genes
02:32Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon...
02:37Gene Duplication and Divergence
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...