CXCL13-producing PD-1^hiCXCR5^- helper T cells in chronic inflammation

CXCL13-producing PD-1^hiCXCR5^-CD4⁺ T cells were discovered in synovial tissues of rheumatoid arthritis (RA). Further intensive analysis of RA samples led to the proposal of PD-1^hiCXCR5^-CD4⁺ T cells as a pathogenic CD4 subset, peripheral helper T (Tph) cells. Tph cells are upregulated also in the peripheral blood of seropositive RA patient and exert B-cell helper activities. Furthermore, Tph cells are associated with other inflammatory conditions including systemic lupus erythematosus, IgG4-related diseases, type 1 diabetes, inflammatory bowel diseases, and malignant tumors. In this review, molecular feature and pathogenic and beneficial functions of Tph cells in inflammatory conditions are discussed.