# Analysis of CCR9, CXCR5 and ICOS in Circulating Follicular Helper T Cell-like Populations in Sjögren’s Disease

**Authors:** Jose Antonio Garcia-Espinoza, Erika Fabiola López-Villalobos, Mariel García-Chagollán, Jefte Felipe Uribe-Martínez, Santiago Torres-Lizárraga, José Francisco Muñoz-Valle, Gloria Esther Martínez-Bonilla, Sergio Cerpa-Cruz, Claudia Azucena Palafox-Sánchez, Miguel Marín-Rosales, Edith Oregon-Romero

PMC · DOI: 10.3390/ijms27041765 · International Journal of Molecular Sciences · 2026-02-12

## TL;DR

The study explores how specific T cells contribute to Sjögren’s disease by analyzing their markers and connections to disease severity.

## Contribution

The study identifies distinct T cell subpopulations and their associations with disease markers in Sjögren’s disease.

## Key findings

- Decreased frequencies of CXCR5+ IL-21+ and CCR9+ IL-4+ T cells were observed in Sjögren’s disease patients.
- Elevated proportions of cTfh-like cells correlated with disease severity and autoantibody production.
- High-dimensional analysis revealed heterogeneous T cell subpopulations in SjD patients.

## Abstract

Circulant follicular helper T cells (cTfh) are a specialized subset of CD4+ T cells that induce immunoglobulin class switching and antibody secretion in plasma cells through the production of IL-21. To investigate the role of cTfh-like cells in the development of Sjögren’s disease (SjD), we analyzed the circulating Tfh-like cells, their production of IL-21 and IL-4, and the co-expression of ICOS, CXCR5, and CCR9 by flow cytometry, and evaluated their association with clinical characteristics of the disease. Percentages of CD4+ IL-21+ CXCR5+ ICOS+ CCR9+ IL-4+ T cells were analyzed in peripheral blood samples from 20 healthy controls (HCs) and 19 patients with SjD. Serum levels of IL-1β, IL-4, IL-6, IL-21, and sCD40L were assessed using a Luminex assay. Laboratory data included anti-Ro/La antibodies, immunoglobulin levels (IgA and IgG), focus score, disease duration, and ESDDAI/SSDDI scores. Decreased frequencies of CXCR5+ IL-21+ T cells and CCR9+ IL-4+ T cells were observed in the peripheral blood of patients with SjD. Heatmap analysis was used to identify correlations between cTfh-like cells and clinical parameters. Elevated proportions of cTfh-like cells were positively correlated with disease severity, inflammatory markers, and autoantibody production. High-dimensional analysis identified distinct subpopulations with differential expression of ICOS, CXCR5, CCR9 and IL-21, suggesting heterogeneity of these cells in SjD and their involvement in disease pathogenesis.

## Linked entities

- **Genes:** CCR9 (C-C motif chemokine receptor 9) [NCBI Gene 10803], CXCR5 (C-X-C motif chemokine receptor 5) [NCBI Gene 643], ICOS (inducible T cell costimulator) [NCBI Gene 29851], IL21 (interleukin 21) [NCBI Gene 59067], IL4 (interleukin 4) [NCBI Gene 3565], IL1B (interleukin 1 beta) [NCBI Gene 3553], IL6 (interleukin 6) [NCBI Gene 3569]

## Full-text entities

- **Genes:** CCL19 (C-C motif chemokine ligand 19) [NCBI Gene 6363] {aka CKb11, ELC, MIP-3b, MIP3B, SCYA19}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, CCL25 (C-C motif chemokine ligand 25) [NCBI Gene 6370] {aka Ck beta-15, Ckb15, SCYA25, TECK, TECKvar}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, ICOSLG (inducible T cell costimulator ligand) [NCBI Gene 23308] {aka B7-H2, B7H2, B7RP-1, B7RP1, B7h, CD275}, MAF (MAF bZIP transcription factor) [NCBI Gene 4094] {aka AYGRP, CCA4, CTRCT21, c-MAF}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNFRSF8 (TNF receptor superfamily member 8) [NCBI Gene 943] {aka CD30, D1S166E, Ki-1}, TRIM21 (tripartite motif containing 21) [NCBI Gene 6737] {aka RNF81, RO52, Ro/SSA, SSA, SSA1, TRIM21/Ro52}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, BCL6 (BCL6 transcription repressor) [NCBI Gene 604] {aka BCL5, BCL6A, LAZ3, ZBTB27, ZNF51}, CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CXCR5 (C-X-C motif chemokine receptor 5) [NCBI Gene 643] {aka BLR1, CD185, MDR15}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, ICOS (inducible T cell costimulator) [NCBI Gene 29851] {aka AILIM, CD278, CVID1}, SSB (small RNA binding exonuclease protection factor La) [NCBI Gene 6741] {aka LARP3, La, La/SSB, SSB/La}, IL7R (interleukin 7 receptor) [NCBI Gene 3575] {aka CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha}, CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CCR9 (C-C motif chemokine receptor 9) [NCBI Gene 10803] {aka CC-CKR-9, CDw199, GPR-9-6, GPR28}, IL21 (interleukin 21) [NCBI Gene 59067] {aka CVID11, IL-21, Za11}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CCR6 (C-C motif chemokine receptor 6) [NCBI Gene 1235] {aka BN-1, C-C CKR-6, CC-CKR-6, CCR-6, CD196, CKR-L3}
- **Diseases:** injury to (MESH:D014947), inflammation (MESH:D007249), SjD (MESH:D012859), atrophy (MESH:D001284), autoimmune disease (MESH:D001327), fatigue (MESH:D005221), hypoxia (MESH:D000860), juvenile dermatomyositis (MESH:D003882), SLE (MESH:D008180), RA (MESH:D001172), ocular and oral damage (MESH:D015817), arthritis (MESH:D001168), salivary (MESH:D012466), dry eyes (MESH:D015352), lymphoma (MESH:D008223), dry mouth (MESH:D014987), hypergammaglobulinemia (MESH:D006942), salivary gland inflammation (MESH:D012793), tissue damage (MESH:D017695)
- **Chemicals:** Brefeldin A (MESH:D020126), Cy5.5 (MESH:C098793), Azathioprine (MESH:D001379), methotrexate (MESH:D008727), AF488 (-), hydroxychloroquine (MESH:D006886), rituximab (MESH:D000069283), prednisone (MESH:D011241), DMSO (MESH:D004121)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941007/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941007/full.md

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Source: https://tomesphere.com/paper/PMC12941007