When individuals fall ill with common respiratory infections such as the cold or flu, subtle yet profound changes occur not only physically but psychologically. Many report feelings of malaise accompanied by depression-like symptoms, social withdrawal, and a pervasive sense of unease. These symptoms, often dismissed as transient side effects of sickness, are increasingly understood to result from the activation of the body’s immune system. Inflammatory signals generated peripherally propagate to the brain, altering neural circuits that govern mood, motivation, and cognition. Engblom’s scientific journey has delved deeply into decoding how peripheral inflammation impacts brain function and how such changes contribute to what is now termed “sickness behavior.”

The phenomenon where immune activation reshapes brain function is not limited to acute infections. Chronic inflammatory disorders such as rheumatoid arthritis and inflammatory bowel disease manifest persistent neurobehavioral symptoms. Engblom’s work investigates the molecular and cellular pathways by which inflammatory mediators communicate with brain cells, shaping behavior and emotional state. His research elucidates how pro-inflammatory cytokines and metabolic changes evoke neurobiological responses that mimic depressive syndromes, thus providing a mechanistic basis for the intersection between immunology and psychiatry.

Engblom emphasizes that understanding these brain-immune interactions transcends academic curiosity. Pinpointing the contributors to illness-induced neurobehavioral alterations opens avenues for targeted therapeutic interventions that could alleviate the psychological suffering accompanying physical disease. Moreover, these insights have broad implications for improving patient care across a spectrum of inflammatory illnesses by integrating neurobiological perspectives into treatment strategies, ultimately enhancing quality of life for affected individuals.

The path that led David Engblom to becoming a trailblazing scientist in neuroimmune research was serendipitous. Initially a medical student, he embarked on research midway through his studies, intending to return to clinical training. However, the allure of discovery and the compelling questions posed by brain-immune crosstalk captivated him profoundly. This unexpected pivot has been met with considerable acclaim, as reflected by numerous prestigious grants and awards recognizing the scientific rigor and impact of his work.

Many in academia will find Engblom’s philosophy about career flexibility inspiring. He advocates for embracing opportunities that arise unexpectedly rather than adhering rigidly to predetermined plans. His own success story exemplifies how openness to diverse experiences and adapting to evolving interests can catalyze significant scientific breakthroughs and career fulfillment. For aspiring researchers, this underscores the importance of intellectual curiosity and resilience in the pursuit of innovation.

In addition to his contributions to research, Engblom has distinguished himself as an exceptional educator. He is extensively involved in teaching medical students, imparting complex neurobiological concepts with clarity and engagement. His pedagogical excellence has earned him the “Kandidat Kork” teaching award multiple times, a testament to his dedication and ability to inspire the next generation of medical professionals. His dual excellence in research and teaching exemplifies the ideal academic role model.

The Onkel Adam Prize, awarded to Engblom, was instituted in 2020 through an endowment from Bengt Normann, a descendant of the eminent 19th-century physician Carl Anton Wetterbergh, who was known by the pseudonym Onkel Adam. The prize aims to foster outstanding medical research at Linköping University while commemorating Wetterbergh’s legacy. With a monetary value of SEK 400,000, this distinction celebrates outstanding scientific accomplishments and encourages continued innovation within the faculty.

Engblom humbly attributes his success to the collective efforts of his research team, underscoring the collaborative nature of modern science. While early in his career he was hands-on with experimental work, he now assumes a role akin to that of a coach guiding a team, helping to steer and mentor his colleagues and students as they execute complex investigations. This leadership fosters an environment in which diverse ideas converge, leading to robust and impactful scientific findings.

His sophisticated investigations employ advanced neurobiological techniques to unravel the intricate dialogue between immune signals and neuronal networks. These methods include molecular assays to profile cytokine expression, in vivo imaging to observe brain activity during inflammatory states, and behavioral paradigms that quantify sickness behaviors in animal models. Such a multidisciplinary approach is crucial in addressing the multifaceted nature of neuroimmune communication pathways.

Engblom’s findings have broader implications extending to the understanding of depression and psychiatric disorders linked to systemic inflammation. By elucidating how inflammatory mediators can precipitate behavioral changes traditionally associated with mental illness, his research bridges the gap between immunology and neuroscience. This integrative perspective could revolutionize how neuropsychiatric symptoms are diagnosed and treated, especially in patients with coexisting inflammatory diseases.

The university’s Faculty of Medicine and Health Sciences, led by Dean Lena Jonasson, praised Engblom’s stellar accomplishments not only in research but also his contributions to education and collegiality. This holistic recognition emphasizes the importance of fostering a vibrant academic community where cutting-edge research is seamlessly integrated with high-quality teaching and collaborative spirit, thereby nurturing an ecosystem where scientific excellence thrives.

David Engblom’s work continues to inspire the scientific and medical communities, illustrating how dedicated inquiry into the brain’s response to systemic inflammation can unravel fundamental mechanisms underlying human sickness behavior. His achievements underscore the critical need to view illness through both biological and psychological lenses, ultimately paving the way for therapies that address the totality of the patient’s experience.

Subject of Research: Neurobiology of brain-immune interactions affecting sickness behavior and neuropsychological symptoms in inflammatory and infectious diseases.

Article Title: Professor David Engblom Awarded 2026 Onkel Adam Prize for Neuroimmune Research on Sickness Behavior

News Publication Date: Not specified in the original content

Web References: https://mediasvc.eurekalert.org/Api/v1/Multimedia/535f9a0f-f0d9-4d45-b3c2-582bf6c99d70/Rendition/low-res/Content/Public

Image Credits: Anna Nilsen/Linköping University

Keywords: Neurobiology, Immune system, Inflammation, Sickness behavior, Cytokines, Neuroimmune communication, Rheumatoid arthritis, Inflammatory bowel disease, Neuropsychiatry, Medical education, Onkel Adam Prize, Linköping University

The first of these studies delves deep into the synaptic aftermath of spinal cord injury using state-of-the-art positron emission tomography (PET) imaging paired with a novel synapse-specific tracer. By employing this tracer in rodent models of mild, moderate, and severe spinal injuries, researchers have achieved unprecedented visualization of synaptic loss and neural communication disruptions. Their longitudinal analysis not only maps structural neural degradation but also correlates in vivo PET findings with meticulous ex vivo biochemical assessments. This integrative approach paves the way for enhanced understanding of the dynamic neurobiological sequelae post-injury and identifies potential molecular targets for therapeutic intervention.

Shifting the focus from localized to systemic, another remarkable study employs whole-body PET combined with sophisticated network-based analytics to unravel the complex crosstalk between the brain and peripheral immune system. Using murine models challenged by infections or pharmacologic agents, the investigators track spatiotemporal shifts in systemic inflammation, revealing intricate pathways of immune modulation across multiple organ systems. By leveraging graph theory and network mapping, this research elucidates how immune responses are coordinated at an organism-wide level, fostering new paradigms in understanding neuroimmune communication and inflammatory diseases.

In the realm of oncology, the convergence of targeted alpha radiation and immunotherapy heralds a promising therapeutic frontier for aggressive lymphoma. Experimental investigations in murine lymphoma models explored the synergistic potential of radiopharmaceuticals delivering alpha particles directly to tumor cells alongside immune checkpoint inhibitors. This dual-modality approach demonstrated superior tumor control, attenuation of immune evasion, and extended survival compared to monotherapies. The strategic combination underscores the capacity of precision nuclear medicine to not only eradicate malignancies but also modulate anti-tumor immunity effectively.

Prostate cancer patients stand to benefit from sophisticated imaging predictors that forecast responsiveness to targeted alpha therapies. A retrospective analysis of advanced prostate cancer cases utilized pretreatment PET scans focusing on prostate-specific membrane antigen (PSMA) uptake patterns. By quantifying tumor burden and tracer distribution, researchers identified imaging biomarkers that correlate with prostate-specific antigen (PSA) kinetics, disease progression risks, and overall survival outcomes. This study underscores the critical role of functional imaging in personalizing radionuclide therapy protocols and optimizing patient-specific treatment plans.

In parallel, comparative assessments of imaging modalities for staging intermediate- and high-risk prostate cancer provide invaluable insights into diagnostic accuracy. By juxtaposing PSMA PET/CT, gastrin-releasing peptide receptor (GRPR) PET/CT, and multiparametric magnetic resonance imaging (mpMRI), investigators benchmarked the sensitivities and specificities of each technique against histopathological findings from surgical specimens. The data reveal nuanced strengths and limitations inherent to these modalities, facilitating evidence-based selection of imaging strategies to improve preoperative staging precision and prognostication of recurrence risk.

Addressing technological innovation, a new deep learning-based method promises to revolutionize PET/CT scan alignment, drastically reducing scan duration and radiation exposure. Tested on next-generation long axial field-of-view PET/CT systems with multiple tracers, this approach maintains essential spatial registration and quantitative accuracy despite shortened acquisition times and ultra-low-dose computed tomography scans. By automating and enhancing image co-registration, this advancement holds transformative potential for clinical throughput, patient comfort, and safety.

Neuroendocrine tumors, often challenging to treat effectively, are the focus of a novel theranostic duo integrating matched imaging and therapeutic radiopharmaceuticals. Early-phase clinical evaluation leveraged single-photon emission computed tomography (SPECT/CT) and dosimetry modeling to optimize tumor visualization and establish radiation dose distributions. Insights gained from this meticulous characterization inform personalized alpha-particle therapy scheduling, maximizing efficacy while minimizing collateral toxicity. This theranostic strategy exemplifies the power of molecular imaging in tailoring precise treatment for complex malignancies.

Collectively, these pioneering studies not only illuminate intricate biological processes but also chart new courses for clinical application, driven by synergy between molecular probes, imaging technologies, and computational analytics. The Journal of Nuclear Medicine remains at the vanguard of disseminating research that bridges fundamental science and patient-centered innovation, fortifying the expanding landscape of theranostics and precision medicine.

The commitment to advancing nuclear medicine as a discipline that offers nuanced visualization and targeted intervention is reflected in the broad spectrum of these investigations—from synaptic mapping in neurological injury to systemic immune profiling and targeted oncologic therapies. As researchers continue refining imaging tracers, radiation delivery methods, and analytic tools, the horizon of personalized healthcare draws nearer.

For practitioners, scientists, and clinicians alike, these insights offer tangible pathways to enhance diagnostic confidence, tailor therapeutic regimens, and ultimately elevate patient outcomes. The fusion of molecular imaging, data science, and immunotherapeutics showcased here exemplifies the vibrant interdisciplinary spirit propelling modern medicine forward.

To explore these advancements in detail, visit The Journal of Nuclear Medicine’s official website, and engage with the community on their social media platforms. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) continues to foster dialogue and innovation, enabling these scientific breakthroughs to transition swiftly from bench to bedside.

Subject of Research: Advanced Molecular Imaging Techniques and Theranostic Applications in Neurology and Oncology
Article Title: Scanning Synapses After Spinal Cord Injury; Brain–Body Immune Cross-Talk Revealed with Whole-Body Imaging; Pairing Alpha Radiation and Immunotherapy for Aggressive Lymphoma; PET Imaging Predictors for Targeted Alpha Therapy in Prostate Cancer; Comparing Imaging Tools to Stage Prostate Cancer; Smarter PET/CT Alignment for Faster, Lower-Dose Whole-Body Imaging; A New Theranostic Pair for Imaging and Treating Neuroendocrine Tumors
News Publication Date: February 6, 2026
Web References:
https://doi.org/10.2967/jnumed.125.271236
https://doi.org/10.2967/jnumed.125.271514
https://doi.org/10.2967/jnumed.125.270515
https://doi.org/10.2967/jnumed.125.270677
https://doi.org/10.2967/jnumed.125.271410
https://doi.org/10.2967/jnumed.125.270420
https://doi.org/10.2967/jnumed.125.270083
Keywords: Molecular imaging, Positron emission tomography, Personalized medicine, Theranostics, Alpha radiation therapy, Prostate cancer imaging, Neuroendocrine tumors, Immune system imaging, PET/CT scan alignment, Radiation dosimetry, Immunotherapy, Neuroimaging

Historically, the central nervous system has been considered an immune-privileged site, with innate immune components such as microglia widely recognized as the primary immune residents. While the meninges and cerebrospinal fluid have been known to harbor immune cells, the presence and role of adaptive immunity within brain tissue remained elusive. This new work decisively demonstrates that CD4+ T cells are not only present within the brain parenchyma but are also transcriptionally and functionally specialized, distinct from their meningeal counterparts.

The subfornical organ, an anatomically and functionally unique circumventricular structure lacking a typical blood-brain barrier, emerges as a critical niche for these brain-resident T cells. Unlike other brain regions, the SFO’s permeable vasculature permits a microenvironment conducive to interaction between circulating immune cells and CNS parenchymal signals. Building on this anatomical peculiarity, the study presents transcriptomic profiling that shows these extravascular T cells express a distinctive set of genes, including the chemokine receptor CXCR6, which mediates their retention and residency within the brain tissue.

Functionally, these αβ T cells exhibit robust production of interferon-gamma (IFNγ), a cytokine pivotal in modulating immune responses and shaping neuronal circuits. Their capacity to secrete IFNγ signifies a departure from classical adaptive immune roles focused merely on pathogen defense. Instead, IFNγ acts in a homeostatic context, influencing neuronal activity and adaptive behaviors, indicating a sophisticated dialogue between immune cells and neural substrates.

Intriguingly, the ontogeny and trafficking of these brain-resident T cells are intimately linked to peripheral immune compartments and their modulation by systemic factors. The research identifies the gut microbiome and white adipose tissue as key sources priming these CD4+ T cells before their migration to the brain. This gut and adipose tissue-derived priming underscores the existence of bidirectional gut-brain and fat-brain axes integral to maintaining CNS equilibrium.

Equally notable is the dynamic regulation of the T cell population within the SFO. Experimental manipulation of the gut microbiota or adipose tissue composition leads to modulation of T cell numbers in the brain, illustrating the adaptability of this immune-brain interface to environmental and metabolic cues. These findings highlight a previously underappreciated systemic influence over central nervous system immune surveillance and neuronal function.

Methodologically, the researchers deployed an unbiased, high-resolution transcriptomic approach that allowed for the comparative characterization of the SFO-resident T cells versus meningeal T cells, solidifying their transcriptional distinctness. This molecular fingerprinting identified unique surface markers and cytokine profiles, reinforcing the concept of tissue-resident lymphocytes specialized for CNS niche-specific functions.

The identification of CXCR6 as a crucial molecule for T cell retention within the SFO opens potential avenues for therapeutic intervention. Modulating the expression or signaling of CXCR6 could provide strategies to influence immune cell localization in neurological diseases where immune dysregulation contributes to pathology. Furthermore, the secretion of IFNγ by these cells implicates a dual role, potentially mediating beneficial neuroimmune interactions or contributing to neuroinflammatory processes under pathological conditions.

This study also sheds light on the enigmatic role of adaptive immunity in regulating behavior. By influencing homeostatic neural circuits, the resident CD4+ T cells within the SFO provide a mechanistic link through which peripheral immune milieu—shaped by diet, microbiota, and adiposity—can influence mood, cognition, and other adaptive behaviors. These findings bridge immunology, neuroscience, and metabolism, highlighting a complex network of systemic regulation.

From a broader perspective, this research reframes our understanding of brain-immune communication by identifying the SFO as a critical immunological nexus interfacing systemic adaptive immunity with central nervous system function. This paradigm shift opens new questions regarding how immune system perturbations might contribute to neuropsychiatric disorders and how restorative manipulation of immune-brain interactions could foster therapeutic innovation.

As investigations continue, the implications of these findings may extend beyond homeostatic regulation into realms of neurodegeneration, infection, and neuroinflammation. The presence of a resident adaptive immune cell population suggests potential roles in surveillance and repair, broadening the therapeutic potential of targeting tissue-resident immune compartments within the CNS.

In summary, the discovery of αβ T cells residing specifically within the subfornical organ—and their pivotal role in modulating CNS homeostasis through IFNγ secretion—marks a transformative milestone in neuroimmunology. Through interdisciplinary approaches integrating immunology, neurobiology, and systemic physiology, this work illuminates new dimensions of brain function regulation, offering exciting prospects for future research and clinical translation.

Subject of Research: Adaptive immune cell residency and function within the brain parenchyma, focusing on CD4+ αβ T cells in the subfornical organ and their role in CNS homeostasis.

Article Title: The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour.

Article References:
Yoshida, T.M., Nguyen, M., Zhang, L. et al. The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour. Nature (2025). https://doi.org/10.1038/s41586-025-09050-7

Image Credits: AI Generated

The cytokine interleukin-17 (IL-17) has garnered particular attention due to its unique duality in the context of brain functionality. Researchers discovered that IL-17 interacts with two disparate brain regions: the amygdala, which processes emotions like fear and anxiety, and the somatosensory cortex, responsible for social behavior. While IL-17’s action in the amygdala can lead to elevated anxiety levels, its effects in the somatosensory cortex seem to foster social engagement, suggesting that hierarchical cytokine actions are intricately woven into behavioral outputs.

The findings elucidate a fascinating interplay where the same immune molecule can precipitate polarizing effects on behavior based on its site of action within the brain. Lead researchers Gloria Choi and Jun Huh explicate how these interactions exemplify a burgeoning field of research where neural and immune responses are not merely coincidental but are deeply interrelated. This relationship is pivotal for understanding how humans and animals process illness beyond just physical symptoms, incorporating emotional and behavioral dimensions as well.

Choi and Huh’s previous work delved into the phenomenon termed the "fever effect," a temporary alleviation of behavioral symptoms in individuals with autism during fever. Their research posited that IL-17 participates in this phenomenon by modulating certain areas in the brain’s cortex. This led the researchers to further examine IL-17’s impact across varying brain structures and delineate its behavioral ramifications more precisely. Their endeavor unveiled the presence of IL-17 receptors, specifically IL-17RA and IL-17RB, within different neuronal populations in the cortex—including the S1DZ area, previously linked to autism-like behaviors.

This detailed receptor mapping is central to understanding how IL-17 governs neuronal excitability, primarily through the action of IL-17E, a variant of IL-17. IL-17E binding to its cortical receptors diminishes neuronal excitability, thereby yielding effects that can mitigate specific behavioral symptoms. This insight advances the hypothesis that IL-17 may have originally evolved as a neuromodulator, with subsequent roles emerging in immune modulation and inflammatory processes over evolutionary timescales.

As the researchers expanded their exploration further into the amygdala, they pinpointed another dimension of IL-17’s influence. The basolateral amygdala (BLA), reputed for its role in emotional processing, was found to harbor a distinct population of neurons responsive to IL-17A and IL-17C. These interactions yield heightened neuronal excitability, which predisposes animals to anxiety, thus imparting a clear link between immune activation and emotional dysregulation. This facet of their findings opens critical perspectives on how immune-related signaling could correlate with mental health issues.

Adding complexity to their findings, the studies revealed that artificially inhibiting IL-17 receptors could inadvertently lead to increased levels of circulating IL-17C. This unexpected result indicates a potential feedback mechanism that could complicate therapeutic strategies targeting IL-17 in clinical settings. Specifically, it raises caution regarding the mental health implications of medications designed to inhibit IL-17 activity, particularly in individuals predisposed to anxiety or mood disorders.

Choi speculates that this anxiogenic response may serve an evolutionary advantage during infections, compelling individuals to isolate themselves to curb the potential spread of pathogens. This behavioral tactic underscores the immune system’s broader role in regulating host behavior, demonstrating that it does not solely operate to combat infections but also to modulate host responses for community protection. Such perspectives could be critical for developing novel therapeutic strategies, enabling scientists to target immune pathways to effect changes in brain functions linked to mood and behavior.

These interconnected studies propose a framework in which immune signaling molecules, specifically cytokines, can yield diverse outcomes concerning brain function. As the research progresses, it becomes evident that context matters—how, where, and when these immune signals engage with neural circuits fundamentally matters to behavioral outcomes. The researchers acknowledge that there is still much mapping to accomplish regarding IL-17 receptors and their corresponding ligands across other regions of the brain.

Ultimately, understanding IL-17 and its receptor variations could illuminate new pathways for addressing neurological disorders, such as autism and depression, by considering immune system modulation as a viable therapeutic avenue. This reframing can inspire researchers to look beyond direct neural interventions, considering instead how systemic immune changes might influence cognitive and emotional health. Through such innovative paradigms, they hope to unveil new therapeutic avenues that intricately align immune function with neurobiology, offering hope for future interventions in mental health.

The interconnectedness between the immune and nervous systems, highlighted by these studies, has opened new avenues for research that may enhance our understanding of psychiatric disorders and their potential correlates with immune function. As these groundbreaking findings settle into the academic discourse, one could speculate on an exciting frontier in research establishment—where the immune system is not merely a defender against disease but a critical mediator of our mental landscapes, shaping who we are in times of health and illness.

The ramifications of this research could rewrite therapeutic strategies, enabling medical and scientific communities to address mental health holistically. Through further explorative studies, it could be plausible to induce beneficial changes in mood or behavior by subtly influencing immune responses, thereby creating a synergy between the immune system’s protective roles and neurological health. The ongoing dialogue within this field proposes an intricate narrative, bridging the gap between immunology and neurobiology, one that promises to deepen our comprehension of what it means to suffer and heal from the complex interplay of immune signals and human emotions.

Subject of Research: Interconnection between immune system and brain behavior via cytokines
Article Title: Inflammatory and anti-inflammatory cytokines bidirectionally modulate amygdala circuits regulating anxiety
News Publication Date: 7-Apr-2025
Web References: DOI link
References: None provided.
Image Credits: None provided.

Keywords: Cytokines, Immune system, Brain behavior, IL-17, Anxiety, Neuromodulation, Amygdala, Somatosensory cortex, Autism, Mental health, Neurobiology, Inflammation.