Increased circulating PD-1hiCXCR5- peripheral helper T cells are associated with disease severity of active ulcerative colitis patients

Immunol Lett. 2021 May:233:2-10. doi: 10.1016/j.imlet.2021.03.001. Epub 2021 Mar 3.


Purpose: A recently identified population of T cells, phenotypically CD4+PD-1hiCXCR5-, has been firstly termed as peripheral helper T cells (Tph) and found to be pathogenic in autoimmune diseases. However, the potential role of Tph in ulcerative colitis (UC) remains unclear. We aim to investigate the changes of circulating Tph in UC patients and their potential significance in the pathogenesis of UC.

Methods: Totally 68 UC patients and 34 age- and sex-matched healthy controls were enrolled. Circulating Tph and B cell subsets were analyzed by flow cytometry. Expressions of inducible T-cell co-stimulator (ICOS) on Tph cells were analyzed. Serum IL-4, IL-10, IL-12 and IL-21 were detected using ELISA. Correlation analyses were conducted between Tph cells and disease severity, functional B cell subsets and serum cytokines.

Results: Both the frequency and absolute number of Tph were significantly increased in active UC patients and ICOS levels in Tph cells were also elevated, compared with remission UC patients and healthy controls. Tph and ICOS expression were significantly positively correlated with Mayo score and serum CRP in active UC patients, and were significantly decreased when achieving remission after treatment. Tph levels were correlated with new memory B cells, plasmablasts, serum IL-4 and IL-21. Meanwhile, serum IL-10 showed negative correlation while IL-12 exhibited positive correlation with circulating Tph cells in UC patients.

Conclusions: Circulating Tph cells are elevated in active UC patients and are associated with the disease activity, which may contribute to the pathogenesis of UC.

Keywords: B lymphocytes; Disease activity; PD-1; Peripheral helper T cells; Ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Biomarkers
  • Colitis, Ulcerative / diagnosis*
  • Colitis, Ulcerative / etiology*
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / therapy
  • Cytokines / metabolism
  • Disease Management
  • Disease Susceptibility
  • Humans
  • Immunoglobulin G / immunology
  • Immunophenotyping
  • Inducible T-Cell Co-Stimulator Protein / genetics
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Lymphocyte Count*
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism*
  • Receptors, CXCR5 / metabolism*
  • Severity of Illness Index
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*


  • Biomarkers
  • Cytokines
  • ICOS protein, human
  • Immunoglobulin G
  • Inducible T-Cell Co-Stimulator Protein
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR5