CD55 characterizes regulatory T cells with reduced functionality and is downregulated in rheumatoid arthritis

Int Immunopharmacol. 2025 Jan 3:145:113822. doi: 10.1016/j.intimp.2024.113822. Epub 2024 Dec 10.

Abstract

Objective: This study aimed to investigate the role of CD55 in regulatory T cells (Tregs) and clarify its clinical relevance in rheumatoid arthritis (RA).

Methods: Flow cytometry was used to examine the expression of Helios and CTLA-4 in CD55 + and CD55- Tregs in mouse peripheral blood and spleen. FoxP3EGFP mice were employed to analyze the in vitro inhibitory function of CD55 + and CD55-Tregs. We compared CD55 expression and function in control and CIA mice. Additionally, the expression of Helios, PD-1, and TIGIT in CD55 + Tregs was examined in healthy controls and RA patients. Correlation analysis and receiver operating characteristic (ROC) curves were used to assess the clinical utility of CD55-related T cell subgroups in RA diagnosis.

Results: High CD55 expression was observed in CD4 + T cells and Tregs, with significantly higher levels in peripheral blood than in the spleen in mice. CD55-Tregs exhibited increased expression of Helios and CTLA-4, and a more pronounced suppressive function compared to CD55 + Tregs in mice. Additionally, CD55 expression in Tregs from peripheral blood and spleen of CIA mice was significantly reduced. In humans, peripheral blood CD55- Tregs expressed higher levels of Helios and TIGIT. Moreover, CD55 + Tregs were markedly reduced in RA patients and correlated with clinical indicators of RA, demonstrating potential as diagnostic markers.

Conclusions: CD55 + Tregs represent a subset of Tregs with weaker functionality and were decreased in RA and could assist the diagnosis of RA.

Keywords: CD4+T cells; CD55; Regulatory T cells; Rheumatoid arthritis, CIA mice.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Arthritis, Rheumatoid* / immunology
  • Arthritis, Rheumatoid* / metabolism
  • CD55 Antigens* / metabolism
  • CTLA-4 Antigen* / genetics
  • CTLA-4 Antigen* / metabolism
  • DNA-Binding Proteins
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Ikaros Transcription Factor* / genetics
  • Ikaros Transcription Factor* / metabolism
  • Male
  • Mice
  • Mice, Inbred DBA
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptors, Immunologic* / genetics
  • Receptors, Immunologic* / metabolism
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes, Regulatory* / immunology
  • Transcription Factors

Substances

  • CD55 Antigens
  • Receptors, Immunologic
  • CTLA-4 Antigen
  • Ikaros Transcription Factor
  • Zfpn1a2 protein, mouse
  • IKZF2 protein, human
  • Forkhead Transcription Factors
  • TIGIT protein, human
  • Programmed Cell Death 1 Receptor
  • T cell Ig and ITIM domain protein, mouse
  • FOXP3 protein, human
  • DNA-Binding Proteins
  • Transcription Factors