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Brain-Infiltrating T Cells Linked to Social Deficits in Autism Mouse Model

Brain-Infiltrating T Cells Linked to Social Deficits in Autism Mouse Model

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The prevalence of autism spectrum disorder (ASD) is roughly one in 36 people, with a male-to-female ratio of 4:1. The disorder is known to be influenced by multiple factors, both genetic (gene mutations and copy number variations) and environmental, such as infections during pregnancy. However, the role of immunity in genetic ASD remains unclear.

One area of interest lies in lymphocytes—cells that are known to shape neurodevelopment and behavior. But their roles in neurodevelopmental disorders are not well defined.

Now, new research shows that a subset of T cells—γδ T cells—can infiltrate the brain and contribute to changes in social behavior in a genetic mouse model that mimics behavioral features of ASD. Depleting these cells from the brain increased sociability, suggesting that targeting abnormal immune function during neurodevelopment may offer interventions for ASD.

This work is published in Science Immunology in the paper, “CXCL16-mediated recruitment of γδ T cells to the brain reduces sociability in mice.”

Infections during pregnancy can induce the release of interleukin-17A (IL-17A) from T helper 17 cells and γδ T cells. Prior research has linked this type of maternal immune activation to neurodevelopmental disorders, but there is a lack of evidence connecting IL-17A and social behaviors in genetic mouse models.

To investigate this further, a team of researchers from the Division of Allergy and Immunology in the Medical Institute of Bioregulation at Kyushu University, in Fukuoka, Japan, studied 15q11-13 duplication (15q dup) mice—a mouse model that mimics a chromosome duplication found in some humans with ASD. These mice also demonstrate reduced social interactions, behavioral inflexibility, and increased anxiety-like behaviors.

The team analyzed immune cell populations in the brains of the 15q dup mice. Their findings suggest an increase in γδ T cells in the developing brains when compared with wild-type mice.

Using single-cell RNA sequencing (scRNA-seq), the team uncovered that this was most likely due to microglia in the brain expressing the chemokine CXCL16, which promotes immune cell migration. CXCL16 was highly expressed in the brains of 15q dup mice and contributed to increased infiltration of γδ T cells.

In addition, experiments revealed that deleting IL-17A–producing γδ T cells or blocking them with antibodies after birth increased sociability and reduced anxiety-like behaviors in the 15q dup mice.

Taken together, the authors note that these findings suggest that “immune dysregulation contributes to social behavior deficits in 15q dup mice, consistent with observations in maternal immune activation models, and may represent a potential target for interventions for ASD-associated differences in social behavior.”

The post Brain-Infiltrating T Cells Linked to Social Deficits in Autism Mouse Model appeared first on GEN – Genetic Engineering and Biotechnology News.

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New webinar: Tackling drug discovery challenges in cancer research

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Cancer cells

Hosted by Drug Discovery World and supported by Sartorius and BioIVT, this webinar will explore the opportunities and challenges that exist within cancer research drug discovery and development.

You will hear from Dr Sudha Rao, Chief Scientific Officer of Kazia Therapeutics, Karol Budzik, PhD, Business Development Associate at Vyriad Therapeutics and Lars van der Veen, Chief Scientific Officer at iOnctura.

Presentations will cover how cancer treatments have shifted towards reprogramming the biology driving tumour growth, immune escape and treatment resistance, the trajectory that in vivo CAR-T treatments are taking, and how challenging tumours burdened by stroma and immune-mediated resistance can be tackled.

Q&A with the speakers follows the presentations.

Register for free now.

The post New webinar: Tackling drug discovery challenges in cancer research appeared first on Drug Discovery World (DDW).

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Psilocybin proves promising in neuropathic pain mouse study

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Amid the rise of psychedelics in the mental health space, researchers have begun to explore psilocybin as a treatment for chemotherapy-induced peripheral neuropathy.

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New Spectrometry Technique Could Aid Formulation Development

New Spectrometry Technique Could Aid Formulation Development

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A new technique combining two forms of spectrometry could help biopharmaceutical companies improve their choice of formulation buffer for antibody manufacturing by revealing how molecular forms and three-dimensional shapes of complex biologics respond to their environment. That’s the view of Christian Bleiholder, PhD, a professor at Florida State University who helped develop the technique.

According to Bleiholder, what happens structurally when a complex biological molecule, such as an antibody or viral spike protein, binds to its target is currently poorly understood.

“This is where [this approach] can help with the bioprocessing and formulation,” he says, as structural changes “can affect the lifespan [of the product] and lead to issues, such as aggregation.”

Because antibodies are complex, existing techniques tend to be powerful at different levels of complexity, he explains. Mass spectrometry is particularly powerful for distinguishing molecular composition, while structural approaches such as X-ray crystallography and cryo-electron microscopy can provide high-resolution structural information.

The challenge is understanding the link between these things within a heterogeneous sample, he says.

To overcome this, Bleiholder and his team worked with Bruker Daltonics to develop Tandem-Trapped Ion Mobility Spectrometry (Tandem-TIMS). This combines tandem ion mobility spectrometry with tandem mass spectrometry to disentangle three overlapping layers of molecular complexity: molecular form, three-dimensional shape, and binding or assembly state, he says.

He explains that, if the proteins have different structures, they can be characterized with tandem ion mobility spectrometry, and then mass spectrometry can be used to look at their molecular forms and binding states.

Going forward, Bleiholder hopes the technique can be used for formulation development but also earlier, during drug discovery of new products, such as multi-specific antibodies, to determine which molecular states are important and how those change when a biologic engages its target. He also plans to look at automating the technique.

Bleiholder spoke about using Tandem-TIMS at the Bioprocessing Summit in Boston earlier this year.

The post New Spectrometry Technique Could Aid Formulation Development appeared first on GEN – Genetic Engineering and Biotechnology News.

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