LdIL-2 treatment in ASD: a novel immunotherapeutic approach targeting Th/Treg dysfunction and neuroinflammation.

Researchers tested a treatment called low-dose IL-2 in mice with autism-like behaviors. The treatment improved social skills and repetitive behaviors by fixing problems with the immune system, specifically increasing helpful immune cells called regulatory T-cells. When these helpful cells were removed, the improvements disappeared. This suggests that autism symptoms might be connected to immune system problems, and fixing these problems could help with autism symptoms.

This preclinical study investigated low-dose interleukin-2 (LdIL-2) as a potential treatment for autism spectrum disorder using BTBR mice, an established autism model. Researchers administered LdIL-2 subcutaneously and assessed autistic-like behaviors through multiple behavioral tests. The treatment significantly improved core autism symptoms and corrected immune imbalances by increasing regulatory T-cells (Tregs) and restoring Th17/Treg and Tfh/Treg balance. Central nervous system inflammation was reduced following treatment.

When Treg cells were experimentally depleted, the behavioral improvements were lost, confirming their crucial role in the therapeutic mechanism. The study suggests LdIL-2 addresses autism symptoms by targeting immune dysregulation, particularly T-cell imbalances. This represents the first investigation of LdIL-2 for autism treatment, showing promise as a novel immunotherapeutic approach.

This preclinical research suggests immunotherapy targeting T-cell imbalances may offer a novel treatment approach for autism. However, extensive human studies are needed before clinical application. The findings support investigating immune dysfunction in autism and developing targeted immunomodulatory treatments.

This is a preclinical study using mouse models, limiting direct applicability to humans. Sample size not reported. Single study without replication. Mechanism of action and long-term effects unclear. Clinical translation requires human safety and efficacy studies.

A significant proportion of children with Autism Spectrum Disorder (ASD) present with immune imbalances. In this study, we sought to alleviate the core symptoms of autism by addressing immune dysregulation, especially T-cell subpopulation imbalances, in BTBR mice through low-dose IL-2 (LdIL-2) treatment. LdIL-2 (30,000 IU) was administered subcutaneously, and changes in autistic behaviors were observed before and after treatment. Behavioral assessments included the three-chamber test, self-grooming test, sniffing test, marble burying test, open field test and Y-maze test.

We also examined alterations in peripheral Th/Treg ratios, cytokine levels, and M1/M2 microglia ratios in the central nervous system via flow cytometry. Neuroinflammatory proteins in cerebrospinal fluid were assessed using proteomic analysis. Furthermore, CD25Treg cells were depleted using PC61, followed by LdIL-2 intervention, to determine the role of Treg cells in LdIL-2-treated BTBR mice. Our results demonstrated that LdIL-2 significantly ameliorated core symptoms of autism in BTBR mice.

LdIL-2 treatment increased Treg cell levels, restored Th17/Treg and Tfh/Treg balance, and corrected immune dysregulation. Central nervous system inflammation was reduced in mice. However, the behavioral improvements were diminished when Treg cells were depleted by PC61. This study represents the first attempt to treat ASD using LdIL-2.

The treatment proved safe and effective in improving both core symptoms and immune imbalances in autism. Symptom improvement was linked to increased Treg cell levels in peripheral blood. LdIL-2 shows potential as a novel therapy for addressing core symptoms of autism.