The Autism Medical & Research Summit (AMRS) is an international, congress dedicated to high-support autism

The immune landscape at the brain’s borders is being reconsidered. In Nature Medicine (2024), we contributed to this broader effort by examining the clinical relevance of immune-brain interactions in patients with glioblastoma.

Since then, accumulating evidence suggests that the skull bone marrow and adjacent meninges form an active immune and hematopoietic compartment directly interfacing with the CNS.

This cranial niche appears to be more than anatomically adjacent – it may actively shape immune surveillance, neuroinflammation, and brain tumor biology.

A key question now is how this interface can be translated into clinical strategies: from refined biomarker approaches and localized immune modulation to new concepts in CNS drug delivery and, potentially, cell-based therapies informed by cranial immune biology.

Selected recent original research:
🔗 Nat Med (2024): https://lnkd.in/efgufXDM
🔗 Cancer Cell (2024): https://lnkd.in/emWxuMv2
🔗 Cell (2026): https://lnkd.in/eAZEGAtq
🔗 Cell (2026): https://lnkd.in/eg4qjubf
🔗 Nat Genet (2026): https://lnkd.in/eDSCYrxQ

#Neuroimmunology #CNS #BrainTumors #CellTherapy #TranslationalResearch

Targeting TREM2 has emerged as an attractive therapeutic strategy for Alzheimer’s disease, with multiple monoclonal antibodies and small-molecule agonists advancing into clinical development in recent years.

TREM2 is a microglial transmembrane receptor that plays key roles in innate immune signaling, microglial survival, and responses to amyloid-β and tau pathology. While early antibody programs have yet to demonstrate clear clinical benefit, they have generated valuable insights into target biology, pharmacology, and clinical trial design.

This target review covers the evolving TREM2 landscape, including lessons from first-generation antibodies, emerging small-molecule agonists, and how recent clinical and patent activity is renewing momentum around this target.

Explore our target review on emerging TREM2 agonists.

Emerging evidence highlights the crucial role of peripheral immune cells in maintaining brain homeostasis and their influence on the pathology of Alzheimer disease (AD). Genome-wide association studies have identified numerous AD risk variants in genes expressed by immune cells, implicating innate and adaptive immune pathways in disease progression. Advances in neuroimmunology have revealed that immune cell crosstalk involving T cells, B cells, monocytes and/or macrophages and neutrophils can modulate the hallmark features of AD, including amyloid plaque accumulation, tau pathology and chronic neuroinflammation. Mechanistic insights suggest that chronic peripheral inflammation, immune exhaustion, metabolic dysfunction and epigenetic reprogramming exacerbate neurodegeneration in AD by promoting toxic inflammation and impairing protein clearance in the brain. These findings may catalyse the development of novel immunomodulatory strategies, such as immune checkpoint inhibition and cytokine targeting, among others, for AD. This Review examines peripheral immune alterations in AD, evaluates related therapeutic opportunities and highlights key knowledge gaps, particularly the need for human-derived data to advance translational progress. Future research should prioritize personalized approaches that integrate genetic risk, immune profiling and ageing to inform next-generation therapies for AD. The importance of peripheral immunity in Alzheimer disease has gained much traction in recent years, mainly due to multiple genome-wide association studies identifying risk loci associated with genes expressed predominantly in the periphery. This review discusses the importance of peripheral immune cells in shaping brain physiology and their role in Alzheimer disease.

Schizophrenia is a challenging and diverse mental health condition with a lifetime prevalence of 0.4%. Schizophrenia usually manifests in late adolescence or early adulthood and is associated with high disability and a reduced life expectancy. Risk factors include genetic predisposition, prenatal and birth complications, infections and immune dysfunction, and cannabis use as well as psychosocial factors such as childhood trauma or migration. The first psychotic episode is often preceded by a long prodromal phase that can last for several years. No markers are yet available for clinical use that allow prediction of disease development or a diagnosis to be established. A leading theory postulates that excitatory–inhibitory (that is, glutamate–GABA) imbalance in the cortex ultimately leads to dysfunction of the dopaminergic system. Schizophrenia is a heterogeneous disease with different manifestations, including psychotic symptoms as well as negative symptoms and global cognitive deficit, that do not respond to antipsychotic drugs, making management very difficult. Pharmacological treatment coupled with psychotherapeutic interventions, such as cognitive behavioural therapy, cognitive remediation and psychoeducation, remains the mainstay of treatment; however, treatment resistance is frequent. The first medication that targets neurotransmitter systems other than dopamine has been approved for use. Current attempts to use virtual reality and avatars to improve psychotic symptoms and smartphone applications to prevent relapses seem promising. Schizophrenia is a complex and often long-lasting mental health condition that typically begins in late adolescence. In this Primer, Leucht and colleagues review the epidemiology of schizophrenia and current understanding of its pathophysiology, diagnosis and treatment, and discuss the quality of life of affected individuals as well as future research directions.

When people viewed virtual avatars with coughs or rashes, their brains triggered an immune response.

Connection and communication between the nervous and immune systems

- Connections between the nervous and immune systems are increasingly recognized as central to brain–body physiology. Rather than operating in isolation, the nervous and immune systems form an integrated network that is more than the sum of its parts.

- The nervous and immune systems perceive and process distinct yet overlapping stimuli from the external and internal environment. The nervous system primarily detects physical cues, including light, sound and touch, whereas the immune system specializes in molecular recognition of pathogens, antigens, cytokines and endogenous damage signals.

- Through bidirectional communication, immune-derived signals modulate neuronal activity, influencing pain, inflammation and sickness behaviours, whereas neural circuits regulate immune cell development and function. Together, these systems act together to orchestrate homeostasis and responses to stress and disease.

- Our understanding of neuroimmune interactions is still in its early stages, but their significance across various diseases is becoming increasingly evident. As research advances, these interactions may offer new therapeutic opportunities.

- For example, inhibiting immune cell trafficking to the brain is already a cornerstone of multiple sclerosis treatment and could soon be extended to psychiatric disorders such as treatment-resistant depression, where abnormal monocyte infiltration into the brain has a role.

https://lnkd.in/eAfce3R7

#immunology #immunesystem #science #neuroimmunology

In a 2025 #ScienceImmunology Review, researchers discussed how interactions between the nervous and immune systems could impact neurological disorders and allergy-related behaviors like food avoidance.

Learn more: https://scim.ag/4jcCmMr #ScienceMagArchives

🎓 Série : Extraits du Congrès "NeuroImmunologie"
🔎 Extrait 5🧠 Encéphalite anti-LGI1 : reconnaître pour traiter tôt
L’encéphalite anti-LGI1(Leucine-Rich Glioma-Inactivated 1), est une forme d’encéphalite auto-immune encore trop souvent diagnostiquée tardivement, alors que son pronostic est excellent si le traitement est initié précocement.
📌 Ce qu’il faut retenir :
✅ Tableau clinique évocateur
Crises faciobrachiales dystoniques (ultra brèves, répétitives, souvent sous-estimées)
Troubles mnésiques récents
Confusion subaiguë
Modifications comportementales
✅ Signal biologique d’alerte
Hyponatrémie fréquente et parfois révélatrice
✅ Examens clés
Anticorps anti-LGI1 (sérum ± LCR)
IRM : hypersignaux temporaux internes
EEG : anomalies temporales
⚠️ Point important : les antiépileptiques seuls sont généralement insuffisants.
👉 L’immunothérapie précoce (corticoïdes, IgIV, plasmaphérèse) change radicalement l’évolution.
👥 Profil typique : homme > 50 ans, mais le diagnostic doit rester ouvert devant tout tableau compatible.
🎯 Message du congrès :
Toute crise faciobrachiale doit faire évoquer une encéphalite auto-immune jusqu’à preuve du contraire.
La reconnaissance précoce évite les séquelles cognitives et améliore significativement le pronostic.
#NeuroImmunologie #EncéphaliteAutoimmune #LGI1 #Neurologie #Médecine #CongrèsMédical #Epilepsie #Neuroinflammation #Dibcenter

New review from our team published in Nature Communications/ Nature Portfolio – “Incorporating meningeal immunity into vaccine development”. We discuss growing evidence that strategies can be developed to deliberately engage meningeal immune compartments, offering new opportunities for immunizations targeting CNS pathogens, optimizing opioid vaccine approaches, and improving our understanding of neuroinflammation.
Open access: https://lnkd.in/ePbrwy8Y 
#Neuroimmunology #VaccineDesign #Adjuvant

Repeated concussions aren’t just “minor” head injuries - they can trigger lasting #braindamage through the #immunesystem.

From contact sports to military training, repeated head impacts increase the risk of #mooddisorders, #memoryloss, movement problems, and neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), seen in former NFL players including Aaron Hernandez. While these risks are well known, the biological mechanisms have remained unclear.

▪️ A team at the Medical University of South Carolina (MUSC) - led by Stephen Tomlinson, PhD and Silvia Guglietta, PhD - has shown that the immune system, specifically the complement system, plays a central role in driving long-term brain damage after repeated mild concussions. The study, led by first author Khalil Mallah, PhD, with Carsten Krieg, PhD, and colleagues including Devin Hatchell (SCTR Institute), was published in Signal Transduction and Targeted Therapy.

▪️ Using a newly developed murine model that mimics repeated concussions in humans, the researchers demonstrated that excessive complement activation over-stimulates #microglia, the brain’s immune cells. Instead of just clearing damaged tissue, these cells begin “over-pruning” synapses and neurons, disrupting brain connectivity and cognition. Importantly, blocking complement activation with an experimental inhibitor (CR2-Crry) reduced inflammation, preserved neurons and synapses, and improved cognitive outcomes.

💡 Why this matters: there are currently no treatments that target the underlying #inflammation following concussion. Because complement inhibitors are already being explored in other diseases, this work opens a realistic path toward disease-modifying therapies to protect athletes, service members, and others exposed to repeated #headinjury.

🗃️ See comments section for reference.

Restless legs syndrome (RLS) and periodic limb movements (PLMs) are increasingly recognized as risk factors for cerebrovascular and cardiovascular diseases, particularly stroke. Conversely, stroke can precipitate or exacerbate the symptoms of RLS and PLMs. This Review explores the shared pathophysiological mechanisms linking RLS and PLMs to cerebrovascular pathology, highlighting a bidirectional relationship. We discuss mechanisms including neurotransmitter dysregulation, autonomic dysfunction, inflammation, oxidative stress, hypoxia and genomic and proteomic factors. Furthermore, we summarize emerging evidence and provide new insights on the potential clinical relevance of RLS in cerebrovascular risk assessment and management. Restless legs syndrome and periodic limb movements are increasingly recognized as risk factors for stroke and other cerebrovascular and cardiovascular diseases and vice versa. This Review explores the shared pathophysiological mechanisms that could underly this bidirectional relationship.

Stroke remains a leading cause of disability owing to the irreversible neuronal loss that it causes and the limited regenerative capacity of the CNS. Although reperfusion therapies such as thrombolysis and mechanical thrombectomy can restore blood flow after stroke, their stringent eligibility criteria leave many patients without treatment options. The immune response, involving complex interactions between brain-resident and peripheral immune cells, has a critical role in stroke recovery. Stem cell-based therapies, particularly those involving neural stem cells and mesenchymal stem cells, may be able to reshape the inflammatory microenvironment after stroke, mitigating secondary injury and promoting tissue repair. However, the precise mechanisms driving their effects remain incompletely understood, hindering clinical translation. In this Review, we highlight the bidirectional crosstalk between stem cells and immune cells (including microglia, T cells and peripheral immune cells) and discuss how these interactions influence neuroinflammation, neural plasticity and circuit remodelling in stroke recovery. We examine key determinants of stem cell therapy efficacy, emphasizing the role of stem cell–immune cell interactions, and discuss targeted strategies to enhance immune modulation and neuroprotection. In this Review, Saef Izzy and colleagues examine the therapeutic potential of stem cells in stroke, with a focus on neural and mesenchymal stem cells. They explore how these stem cells interact with brain immune cells to modulate the inflammatory microenvironment, restore blood–brain barrier integrity and promote tissue repair following a stroke.

In a 2024 Science study, researchers reported a previously overlooked contributor to the meningeal immune landscape in early brain development: group 2 innate lymphoid cells (ILC2s).

Learn more in this #SciencePerspective: https://scim.ag/44oK8y1 #ScienceMagArchives

Epidemiological data have identified Epstein–Barr virus (EBV) infection as the main environmental risk factor for multiple sclerosis, the predominant autoimmune disease of the central nervous system (CNS)1. However, how EBV infection initiates multiple sclerosis pathogenesis remains unclear. Here we demonstrate that EBV expands oligoclonal T-bet+CXCR3+ B cells that home to the CNS in humanized mice. Effector memory CD8+ T cells and CD4+ TH1 cells as well as CD4+ TH17 cells co-migrate to the brain of EBV-infected humanized mice. T-bet+CXCR3+ B cells can colonize submeningeal brain regions in the absence of other lymphocytes and attract T cells. Depletion of B cells with rituximab or blocking of CXCR3 significantly decreases lymphocyte infiltration into the CNS. Thus, we suggest that symptomatic primary EBV infection generates B cell subsets that gain access to the CNS, attract T cells and thereby initiate multiple sclerosis. Epstein–Barr virus infection generates a neuroinvasive B cell subset, which recruits activated T cells to the central nervous system, promoting multiple sclerosis.

Understanding the Neurologic Impact of Influenza and the Protective Role of Vaccination 🫁 🧠

Influenza is widely recognized as a respiratory infection affecting people across all age groups, leading to substantial illness and death. While respiratory complications are well known, the nonpulmonary effects—particularly neurologic complications—are often overlooked.

Neurologic issues such as seizures, encephalitis, myelitis, and Guillain-Barré Syndrome can occur during acute influenza infections, though these are relatively rare. More concerning, however, is emerging evidence linking influenza with long-term risks like stroke and dementia—two of the leading causes of death and disability worldwide.

💉 Encouragingly, recent studies suggest that influenza vaccination may offer protective benefits beyond preventing flu itself, potentially reducing the risk of stroke and dementia.
This highlights the importance of flu vaccination not only for respiratory health but also for protecting our brain health.

https://lnkd.in/emQnFrHd

#Influenza #Neurology #PublicHealth #Vaccination #StrokePrevention #DementiaAwareness #Healthcare

While caring for a patient with pancreatic cancer during medical school, HMS alum William Hwang was surprised to learn that malignant cells can surround and invade nerves — a painful phenomenon known as perineurial invasion.

“I wondered why cancer cells would form such intimate connections with nerves,” he recalls. “What do they derive from this relationship, and how can we intervene?”

Now an HMS professor of radiation oncology at Massachusetts General Hospital, Hwang is helping to pioneer a new field known as cancer neuroscience. His lab uses spatial transcriptomics — an approach that combines advanced imaging with RNA sequencing and complex algorithms analyzing massive data sets — to pinpoint the genes expressed within individual cells in different areas of a tumor. These new techniques help his team identify differences between tumor cells that are engaged with nerves and those that aren’t.

Growing cancer cells together with nerves in dishes, Hwang’s team recently identified molecules produced by cancer cells that encourage nerves to grow toward and invade tumors. They’re now figuring out how to intervene in this process to prevent cancer cells from invading nerves, ultimately improving outcomes for patients. | 11 comments on LinkedIn