The Role of Natural Killer Cells in Autoimmune Diseases

Christel Payseng
6 min readNov 28, 2023

Natural killer (NK) cells, discovered in the early 1970s, are integral members of the innate immune system. Originally known for their potent cytotoxicity against virus-infected cells and anti-tumoral responses, these cells are now recognized for their influence on both innate and adaptive immunity. Unlike T or B cells, NK cells lack T or B cell receptors and are classified into subgroups based on their expression of CD16 and CD56. They bridge the gap between innate and adaptive immunity, contributing to immune regulation through cytokine production and cytotoxic functions.

The delicate balance of cell-surface receptors, cytokines like IL-2, IL-12, and IL-15, and NK-derived cytokines modulate immune responses and play a role in various immune-mediated diseases.

Autoimmune conditions such as ankylosing spondylitis, multiple sclerosis, rheumatoid arthritis, and type-1 diabetes have been associated with dysregulated NK cell functions. The dysfunction of NK cells in these disorders may arise from various mechanisms, including genetic factors, aberrant immune responses, or impaired regulatory functions of NK cells.

NK cells’ contribution to autoimmune diseases is multifaceted. They not only participate in the initial immune response but also influence disease progression and resolution. Studies suggest that certain genes associated with autoimmune disorders might affect NK cell functions, leading to uncontrolled T cell responses and contributing to disease pathology. Furthermore, NK cells’ association with type-1 interferon, a crucial component of anti-viral responses, further underscores their role in autoimmune conditions.

Understanding the intricate role of NK cells in autoimmune diseases is essential for potential therapeutic interventions.

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As these cells serve as a connection between the innate and adaptive immune systems, their involvement in inflammation and immune regulation warrants comprehensive investigation. While significant progress has been made in comprehending NK cell biology, a deeper understanding is crucial for leveraging these versatile cells in innovative therapeutic approaches.

This review delves into the diverse facets of NK cell biology, their role in immune responses, and their involvement in autoimmune disorders. It sheds light on their development, maturation, receptors, transcriptional profiles, effector functions, and mechanisms of cytotoxicity. Recent advances in RNA sequencing techniques have enabled a more comprehensive understanding of the gene expression profiles and functions of NK cells, providing insights into their roles in autoimmune conditions such as type-1 diabetes and lupus nephritis.

Efforts to decode the transcriptional regulation of NK cells during their development and activation have revealed critical insights into their functions. Notably, studies have highlighted the involvement of specific genes and signaling pathways associated with NK cell function in autoimmune diseases. Understanding these molecular mechanisms could pave the way for novel therapeutic targets.

NK cells exhibit two fundamental effector functions: direct cell killing and cytokine production. They exert cytotoxicity against abnormal cells through multiple mechanisms, including the activation of death receptors, release of cytolytic granules containing perforin and granzymes, and induction of apoptotic pathways. This cytotoxicity is crucial for eliminating infected or transformed cells, and safeguarding the body from potential threats.

In summary, NK cells’ intricate role in the immune system, their contribution to autoimmune diseases, and their potential as therapeutic targets represent a promising area for further research. Advancements in understanding their biology and functions offer prospects for innovative interventions in autoimmune disorders, emphasizing the need for continued exploration in this field.

Multiple Sclerosis: Unveiling the Role of NK Cells

Multiple sclerosis (MS) is a multifaceted disorder of the central nervous system marked by chronic inflammation, demyelination, and neural damage. While its autoimmune origins, influenced by genetic predisposition and environmental factors, are acknowledged, recent studies emphasize the intricate role of natural killer (NK) cells in the disease’s progression.

NK cells, known for their diverse activities, play a pivotal yet contentious role in MS. Some studies suggest their involvement in both exacerbating and mitigating the condition, contributing to the complex pathology.

The intricate interplay between NK cells and immunological receptors (NKRs) has garnered attention. The expression profiles of NKRs, such as killer cell immunoglobulin-like receptors (KIRs) and the CD94:NKG2A complex, unveil potential implications in MS. For instance, deficiencies in certain KIRs or their ligands were found in MS patients, suggesting altered NK cell functions. However, the roles of various KIR allelic variants require deeper exploration for a comprehensive understanding.

NK cell activities are also intertwined with the modulation of autoimmune mechanisms and viral defense. Their cytotoxic potential extends to controlling autoreactive T cells, antigen-presenting cells (APCs), and viral infections, posing both protective and detrimental effects. Notably, their impaired cytotoxicity in MS patients has been associated with disease progression and manifestation, underscoring the significance of NK cells in MS pathophysiology.

Linking Viral Infections and NK Cells in MS

Viral infections, notably Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus (HHV)-6, have been implicated in MS pathogenesis through molecular mimicry. NK cells serve as early defenders against viral infections, highlighting their potential role in preventing MS development. Paradoxically, the association between decreased NK cell cytotoxicity and MS attacks suggests a multifaceted influence on disease progression.

The CD56bright Subset and NK Cell Functionality

Exploration of the CD56bright NK cell subset reveals intriguing nuances in MS. While their frequencies might not differ significantly between healthy individuals and untreated MS patients, treatments like IFN-β derivatives, daclizumab, and alemtuzumab have been associated with increased CD56bright NK cell levels. However, functional assays suggest a potential impairment in their cytokine secretions and cytotoxicity, hinting at their complex and perhaps context-dependent roles in MS pathogenesis.

Conclusion

NK cells present a dichotomous role in MS, demonstrating both protective and exacerbating effects. Their intricate interplay with various receptors, involvement in viral defense, and functional diversity underscore their significance in MS pathology. Further investigations are imperative to unravel the precise roles of NK cells in different disease stages and their potential as therapeutic targets in MS management.

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She wrote the book Scripted in Heaven, I Called Myself Cassandra, and has an upcoming book When Silence is not Golden, a book about Autism Spectrum Disorder and the New Breed of Homo Sapiens.

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Source Credit:

https://www.frontiersin.org/articles/10.3389/fimmu.2017.01124

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Christel Payseng

Writer, PR Media, Literature Hobbyists, Digital Marketer