tetano
Editor, Senior Moderator
Front Immunol
. 2025 Jun 20:16:1606115.
doi: 10.3389/fimmu.2025.1606115. eCollection 2025. Sex-based immunological differences in multisystem inflammatory syndrome in children: potential role of T[SUB]R3-56[/SUB] cells for pathogenesis, diagnosis, and therapy
Flavia Carriero[SUP] #[/SUP][SUP] 1 [/SUP], Monica Gelzo[SUP] #[/SUP][SUP] 2 3 [/SUP], Valentina Rubino[SUP] 4 [/SUP], Giulia Scalia[SUP] 2 [/SUP], Alice Castaldo[SUP] 5 [/SUP], Vincenzo Tipo[SUP] 5 [/SUP], Antonietta Giannattasio[SUP] 5 [/SUP], Carolina D'Anna[SUP] 5 [/SUP], Giuseppina Ruggiero[SUP] #[/SUP][SUP] 4 [/SUP], Giuseppe Castaldo[SUP] #[/SUP][SUP] 2 3 [/SUP], Giuseppe Terrazzano[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
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 T[SUB]R3-56[/SUB] lymphocytes, a novel population of regulatory T cells. Our findings reveal a positive correlation between circulating T[SUB]R3-56[/SUB] 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 T[SUB]R3-56[/SUB] 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 T[SUB]R3-56[/SUB] 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.
Keywords: MIS-C; TR3-56 cells; Treg; biomarkers; immune regulation; sex-based differences.
. 2025 Jun 20:16:1606115.
doi: 10.3389/fimmu.2025.1606115. eCollection 2025. Sex-based immunological differences in multisystem inflammatory syndrome in children: potential role of T[SUB]R3-56[/SUB] cells for pathogenesis, diagnosis, and therapy
Flavia Carriero[SUP] #[/SUP][SUP] 1 [/SUP], Monica Gelzo[SUP] #[/SUP][SUP] 2 3 [/SUP], Valentina Rubino[SUP] 4 [/SUP], Giulia Scalia[SUP] 2 [/SUP], Alice Castaldo[SUP] 5 [/SUP], Vincenzo Tipo[SUP] 5 [/SUP], Antonietta Giannattasio[SUP] 5 [/SUP], Carolina D'Anna[SUP] 5 [/SUP], Giuseppina Ruggiero[SUP] #[/SUP][SUP] 4 [/SUP], Giuseppe Castaldo[SUP] #[/SUP][SUP] 2 3 [/SUP], Giuseppe Terrazzano[SUP] #[/SUP][SUP] 1 [/SUP]
Affiliations
- PMID: 40621459
- PMCID: PMC12226297
- DOI: 10.3389/fimmu.2025.1606115
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 T[SUB]R3-56[/SUB] lymphocytes, a novel population of regulatory T cells. Our findings reveal a positive correlation between circulating T[SUB]R3-56[/SUB] 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 T[SUB]R3-56[/SUB] 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 T[SUB]R3-56[/SUB] 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.
Keywords: MIS-C; TR3-56 cells; Treg; biomarkers; immune regulation; sex-based differences.