Autoinflammatory & rare systemic diseases

CCR4+Tfh2 cells specifically produce IL-4 driving the pathological reaction in IgG4-related disease

Clin Exp RheumatolPublished Mechanistic study

Authors' conclusion

CCR4 serves as a marker for identifying Tfh2 cells that specifically produce IL-4. CCR4+Tfh2 cells are a widely present T cell population that infiltrates tertiary lymphoid tissues and storiform fibrosis of IgG4-RD.

Study context

Population
Treatment-naïve patients with active IgG4-related disease (IgG4-RD)IgG4-RD patients
Participants
23 patients
Comparison
IgG4-RD vs healthy controls; CCR4+Tfh2 vs CCR4-Tfh2 cells
  • IgG4-RDn = 23
Outcome
Whether CCR4 identifies IL-4-producing Tfh2 cells and its involvement in IgG4-RD
Methodological detailsmulti-colour flow cytometry, t-SNE, immunohistochemical staining
  • Multi-colour flow cytometry
  • t-SNE
  • Immunohistochemical staining

Main finding

As reported in the abstract

  • Tfh2 cells expressing CCR4 were identified as T follicular helper (Tfh) cells that specifically produce IL-4
  • CCR4+Tfh2 cells showed higher GATA-3 and ICOS expression than CCR4-Tfh2 cells; no difference in BCL-6 and FOXP3
  • Proportion of CCR4+Tfh2 cells in peripheral blood increased in IgG4-RD vs healthy controls; even more infiltrated affected lesions
  • CCR4+GATA-3+Tfh2 cells diffusely infiltrated tertiary lymphoid tissues and storiform fibrosis lesions
  • Proportion of CCR4+Tfh2 cells correlated significantly, specifically with serum IgG4 levels among clinical indicators

Further findings

Effect of GC therapy on CCR4+Tfh2 cells

GC therapy did not correct the increased proportion of CCR4+Tfh2 cells

Original publication

CCR4+Tfh2 cells specifically produce IL-4 driving the pathological reaction in IgG4-related disease. Clin Exp Rheumatol. Published 28 May 2024. doi:10.55563/clinexprheumatol/me9o6d

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