Illustration of dendritic cells with Dlg2 protein intertwined.

Decoding Your Immune System: The Surprising Role of Dlg2 in Fighting Infections

Rhea Morgan in Science & Nature August 2025 • 5 min read.

"Scientists uncover a new form of Dlg2 that could revolutionize how we understand and treat immune responses, especially in those fighting off viral infections."

Our immune system is a complex network, constantly working to protect us from harm. Among its many components, dendritic cells (DCs) play a vital role. Think of them as the scouts of our immune system, identifying threats and signaling the troops to action. Within the DC family, plasmacytoid dendritic cells (pDCs) are the specialized rapid responders, particularly skilled at producing large amounts of type I interferons (IFNs) to fight off viral infections.

For years, scientists have been unraveling the intricacies of these immune cells, seeking to understand how they function and how we can better harness their power. Now, a new study has shed light on a previously underappreciated protein called Dlg2 and its surprising role in the function of these crucial pDCs.

The groundbreaking research has identified a novel variant of Dlg2, revealing how it operates differently within pDCs. This discovery not only enriches our understanding of the immune system but also opens new avenues for potential therapeutic interventions. Imagine being able to fine-tune our immune responses to more effectively combat viral invaders – this research brings that future closer than ever.

What Is Dlg2 and Why Should You Care?

Illustration of dendritic cells with Dlg2 protein intertwined.

Dlg2, or Discs large homolog 2, is a member of the MAGUK (membrane-associated guanylate kinase) protein family. These proteins are like molecular organizers, bringing together receptors and signaling molecules on cell membranes. In the brain, Dlg2 helps cluster important channels and receptors at synapses, which are critical for nerve cell communication. Until now, its role in immune cells was largely unknown.

The recent study, published in BMC Genomics, reveals that Dlg2 is highly expressed in pDCs, specifically those producing type I IFNs like IFNβ. The researchers identified a novel splice variant of the Dlg2 gene, which they termed Dlg2n, and found that it is uniquely expressed in these IFNβ-producing pDCs after stimulation. This discovery suggests that Dlg2 plays a more significant role in our immune responses than previously understood.

Novel Splice Variant: The identification of Dlg2n, a new form of Dlg2, adds a new layer to our understanding of gene expression in immune cells.
IFNβ Production: Dlg2's heightened presence in IFNβ-producing pDCs highlights its importance in antiviral immune responses.
Unique Expression: Unlike other immune or brain cells, pDCs feature a distinctive Dlg2 splicing pattern, emphasizing their specialized nature.

The study further explored the localization of different Dlg2 isoforms within cells, revealing that while the larger isoform DLG2α1 is found at the plasma membrane, the newly identified DLG2n, along with DLG2γ, is distributed throughout the cytoplasm and even in the nucleus. This suggests that DLG2n might have a direct impact on gene expression within the cell's control center.

What Does This Mean for Future Treatments?

This research opens exciting new possibilities for immunotherapy, the strategy of harnessing the immune system to fight disease. Understanding the specific role of Dlg2n in pDCs could lead to the development of targeted therapies that boost the body's natural ability to combat viral infections. While much remains to be explored, this discovery marks a significant step forward in our quest to unlock the full potential of the immune system. The newly identified Dlg2n isoform presents a promising avenue for future research and therapeutic development, offering hope for more effective strategies against viral diseases and other immune-related conditions. Further studies are needed to fully elucidate the functional role of this isoform in pDCs and other myeloid cells, as well as neurons, but the initial findings are undoubtedly encouraging.

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This article is based on research published under:

DOI-LINK: 10.1186/s12864-018-4573-5, Alternate LINK

Title: Identification Of A Novel Dlg2 Isoform Differentially Expressed In Ifnβ-Producing Plasmacytoid Dendritic Cells

Subject: Genetics

Journal: BMC Genomics

Publisher: Springer Science and Business Media LLC

Authors: Shafaqat Ali, Alexander Hoven, Regine J. Dress, Heiner Schaal, Judith Alferink, Stefanie Scheu

Published: 2018-03-12

Everything You Need To Know

What is the primary function of plasmacytoid dendritic cells (pDCs), and how does Dlg2 relate to this function?

Plasmacytoid dendritic cells (pDCs) are specialized immune cells critical for producing type I interferons (IFNs), like IFNβ, to combat viral infections. The recent discovery highlights that Dlg2, specifically a novel splice variant called Dlg2n, is highly expressed in these IFNβ-producing pDCs after stimulation, suggesting that Dlg2 plays a more significant role in antiviral immune responses than previously understood. Dlg2n potentially enhances the pDCs ability to fight infections by influencing gene expression.

How does the newly discovered Dlg2n isoform differ from other known Dlg2 isoforms, and what are the implications of these differences?

The newly identified Dlg2n isoform differs from the larger DLG2α1 isoform in its cellular localization. While DLG2α1 is found at the plasma membrane, DLG2n, along with DLG2γ, is distributed throughout the cytoplasm and even in the nucleus. This difference suggests that DLG2n might directly impact gene expression within the cell's control center, potentially fine-tuning the immune response. This is in contrast to DLG2α1, which likely plays a role at the cell membrane.

What are membrane-associated guanylate kinase (MAGUK) proteins, and how does Dlg2 fit into this protein family?

Membrane-associated guanylate kinase (MAGUK) proteins are molecular organizers that bring together receptors and signaling molecules on cell membranes. Dlg2, or Discs large homolog 2, is a member of this family. In the brain, Dlg2 helps cluster important channels and receptors at synapses, which are critical for nerve cell communication. The recent study extends our understanding by revealing its role in immune cells, particularly in pDCs, where the Dlg2n variant contributes to antiviral immune responses.

How could understanding the role of Dlg2n in plasmacytoid dendritic cells (pDCs) lead to new immunotherapies?

Understanding the specific role of Dlg2n in pDCs could lead to the development of targeted immunotherapies designed to boost the body's natural ability to combat viral infections. By fine-tuning the activity of Dlg2n, it may be possible to enhance the production of type I interferons (IFNs) and improve the overall antiviral immune response. This presents a promising avenue for future research and therapeutic development, offering hope for more effective strategies against viral diseases and other immune-related conditions.

What further research is needed to fully understand the functional role of the Dlg2n isoform, and why is it important?

Further studies are needed to fully elucidate the functional role of the Dlg2n isoform in pDCs, other myeloid cells, as well as neurons. Understanding how Dlg2n impacts gene expression and the production of type I interferons (IFNs) is critical. Determining the precise mechanisms by which Dlg2n influences the immune response could reveal new therapeutic targets for viral infections and other immune-related conditions. Exploring its role in different cell types may provide insights into broader biological functions of Dlg2n beyond antiviral immunity.