CHARACTERIZATION OF CCR8+ REGULATORY T CELLS IN RHEUMATOID ARTHRITIS

CRISTINA ACOSTA; LUISINA ONOFRIO; PAOLA FERRERO; EDUARDO MUSSANO; LAURA ONETTI; ISAAC CADILE; AGUSTINA GARCÍA ORO; SANTIAGO BOCCARDO; CAROLINA MONTES; ADRIANA GRUPPI; EVA ACOSTA RODRÍGUEZ

San Luis

Congreso; LXXI Reunión Anual de la Sociedad Argentina de Inmunología; 2023

SAI

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory diseasecharacterized by joint destruction. In RA, immunoregulatory mechanisms mediatedby Foxp3+ regulatory T cells may play fundamental roles but are poorly explored.The Treg compartment is heterogeneous, comprising several specializedsubpopulations. Among them, CCR8+ Treg cells show enhanced suppressioncapacity and tissue repair functions that endows them with a detrimental role incancer. The role of specialized Treg subsets in RA is unknown. We aimed study thephenotypic and functional characteristics of CCR8+ Treg cells in RA patientsdetermining their protective or pathogenic role.We studied 53 patients diagnosed with RA according to ACR/EULAR 2010classification criteria at the Hospital Nacional de Clínicas de Córdoba (24 untreated,17 with synthetic DMARDs, 12 with biological DMARDs). Thirty healthy individualsage- and sex- matched were recruited as controls (HD). RA activity was assessedby the DAS28 index. Frequencies of Treg cells (CD3+CD4+CD25+FoxP3+) andCCR8+ Treg cells was measured by flow cytometry in cryopreserved mononuclearcells isolated from peripheral blood and synovial fluid (SF). Phenotypiccharacterization of CCR8+ Treg cells included the expression of regulatorymolecules (CTLA-4, TIGIT, ICOS, CD39, and CD73) and tissue repair profile (GATA-3). Serum levels of CCL1, the CCR8 ligand, were measured by ELISA.We found that Treg cell frequency was slightly but significantly higher in the PBMCfrom patients versus controls (RA 4,41 ±1,81 vs HD 3,72 ± 1,30; p 0.046), while thefrequency of the CCR8+ subset was similar between the two groups (RA 6.94 ± 3.77vs HD 7.14 ± 2.99). Phenotypic characterization showed similar expression of CTLA-4, TIGIT, ICOS, CD39, CD73, and GATA-3 between CCR8+ Treg cells of RA andHD. Also serum levels of CCL1 were similar in RA and HD, and showed nocorrelation with the frequency of peripheral CCR8+ Treg cells. An initial functionalevaluation determined lack of correlation between the percentages of Treg orCCR8+ Treg cells and the expression of IL-2, TNF, CD107, and CD57 in memoryCD4+ and CD8+ T cells in RA and HD. Accordingly, percentages of Treg and CCR8+Treg cells in RA showed no correlation with DAS28. Of note, CCR8+ Treg cellsappeared to be increased in SF, where their frequency ranged between 18.5 and39.4, (n=4).Altogether, we showed that, despite exhibiting increased peripheral Treg cells, RApatients present a conserved CCR8+ Treg cell frequency. No correlations werefound between Treg cells and CCR8+ Treg cells frequencies and production ofimmune effector mediators or overall disease scores. The higher occurrence ofCCR8+ Treg cells in LS suggests a likely preferential migration and enrichment intissues. A deeper characterization of the CCR8+ Treg cell population in RA patients,including functional and transcriptomic evaluation, would allow us to better delineatethe possible function of this subset in RA.