American Society of Hirudotherapy

Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children

Research article published in Nature communications (2021)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Research reportSafety & Infection ControlBeckmann ND et al. · Nature communications, 2021

Abstract

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, N.I.H., Extramural
Indexed MeSH termsAdolescentCD56 AntigenCD57 AntigensCD8-Positive T-LymphocytesCOVID-19ChildChild, PreschoolDown-RegulationFemaleHumansInfantInfant, Newborn

Summary

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Why This Matters for Hirudotherapy

This study performed RNA sequencing of blood from patients with multisystem inflammatory syndrome in children (MIS-C) and controls, identifying a co-expression module annotated to CD56dimCD57+ NK cells and exhausted CD8+ T cells, with TBX21 as a key regulator. A similar transcriptomic signature was found in Kawasaki disease. The study implicates downregulation of NK cells and cytotoxic T cell exhaustion in MIS-C pathogenesis. The article contains no mention of leeches, hirudotherapy, hirudin, or any leech-derived substance. There is no defensible connection to ASH's domain of hirudotherapy or the leech secretome. The subject matter—pediatric post-infectious inflammatory immunopathology—is unrelated to medicinal leech therapy, and this article is not relevant for the ASH research library.

Citation

Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children

Beckmann ND et al. · Nature communications, 2021

DOI

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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