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Updated: Jan 23, 2026
Analysis of Human Natural Killer Cell Metabolism
Published on: June 22, 2020
Complete sequence analysis of human toll-like receptor 3 gene in natural killer cells of multiple sclerosis patients
Elie Deeba1, Dana Koptides2, Anastasia Lambrianides3
1Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Background:
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) where both environmental and genetic risk factors play a role. Among the environmental risk factors, EBV and HSV infections have been suggested as strong candidates contributing to MS pathology/progression. Viral recognition and control is largely tasked to the NK cells via TLR recognition and various cytotoxic and immunoregulatory functions. The present work aimed to characterize NK cells isolated from MS patients for genetic polymorphisms in the gene encoding for TLR3, as TLR3 in NK cells is important in herpesvirus recognition.
Methods:
Highly purified NK cells isolated from peripheral blood of MS patients (n = 27) and healthy controls (n = 30) were used to sequence all five exons of the TLR3 gene using sanger sequencing. Alignment of the obtained sequences with the wild-type TLR3 sequence was used to identify genetic polymorphisms within the TLR3 gene.
Results:
The alignment identified multiple substitution mutations across the five exons of the TLR3 gene (rs116729895, rs3775296, rs377529, rs3775290, rs3775291, rs376735334 and rs73873710). A significant difference was observed in the allele distribution of rs3775291 (Leu412Phe) between MS patients and HC, whereby the minor allele was detected in 38.9% of MS patients versus 11% of HC (Fisher's exact test, p = 0.021).
Conclusion:
There appears to be a possible association between the TLR3 missense mutation rs3775291 and multiple sclerosis, which might be attributed to changes in the TLR3 functional properties.
Insights
Genetic variations in the Toll-like receptor 3 (TLR3) gene may be associated with multiple sclerosis (MS). A specific TLR3 mutation (rs3775291) was found more frequently in MS patients, suggesting a potential role in disease development.
Area of Science:
- Immunology
- Neuroscience
- Genetics
Background:
- Multiple sclerosis (MS) is a central nervous system demyelinating disease influenced by genetic and environmental factors.
- Epstein-Barr virus (EBV) and herpes simplex virus (HSV) infections are implicated in MS pathology.
- Natural killer (NK) cells play a crucial role in viral recognition and immune control via Toll-like receptor 3 (TLR3).
Purpose of the Study:
- To investigate genetic polymorphisms in the TLR3 gene within NK cells of MS patients.
- To explore the potential association between TLR3 gene variations and susceptibility to MS.
Main Methods:
- Purified NK cells were isolated from 27 MS patients and 30 healthy controls.
- All five exons of the TLR3 gene were sequenced using Sanger sequencing.
- Sequences were aligned to identify genetic polymorphisms compared to the wild-type TLR3 sequence.
Main Results:
- Multiple substitution mutations were identified in the TLR3 gene of MS patients and controls.
- A significant difference in allele distribution was observed for the rs3775291 polymorphism (Leu412Phe) between MS patients (38.9%) and healthy controls (11%).
- The minor allele of rs3775291 was more prevalent in MS patients (p=0.021).
Conclusions:
- A potential association exists between the TLR3 missense mutation rs3775291 and multiple sclerosis.
- This association may be linked to altered functional properties of TLR3 in MS pathogenesis.
- Further research is warranted to elucidate the functional impact of this TLR3 variant in MS.
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