# Sex-based immunological differences in multisystem inflammatory syndrome in children: potential role of TR3–56 cells for pathogenesis, diagnosis, and therapy

## TL;DR

The study explores how immune responses differ between boys and girls with a rare inflammatory disease in children, focusing on a specific type of regulatory T cell that may help in diagnosis and treatment.

## Contribution

The study identifies sex-based differences in immune responses and highlights the potential role of TR3–56 cells in MIS-C pathogenesis and therapy.

## Key findings

- Male MIS-C patients have higher TR3–56 lymphocytes and T cell activation markers linked to severe disease.
- Female patients show stronger immune memory and regulatory responses, possibly reducing inflammation.
- TR3–56 cells correlate with regulatory T cells and may serve as biomarkers or therapeutic targets.

## Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) is characterized by immune dysregulation, exhibiting clinical and immunological features reminiscent of autoimmune processes, although its underlying mechanisms remain incompletely understood. This study examines immune system alterations in MIS-C patients, focusing on TR3–56 lymphocytes, a novel population of regulatory T cells. Our findings reveal a positive correlation between circulating TR3–56 cells and regulatory T cells, suggesting a potential immunoregulatory role in MIS-C pathogenesis. Furthermore, we identified significant sex-based differences in immune responses. Male patients exhibit higher percentages of TR3–56 lymphocytes and increased expression of T cell activation markers, which correlate with greater disease severity. Conversely, female patients display immune profiles characterized by stronger immune T cell memory and regulatory responses, potentially helping to modulate inflammation. These findings highlight the relevance of considering sex-based differences in immune responses to MIS-C and suggest that TR3–56 lymphocytes may serve as novel biomarkers and potentially as therapeutic targets. Our study enhances the understanding of immune dysregulation in MIS-C and underscores the need for sex-specific therapeutic strategies to improve patient outcomes.