The CC chemokine receptor 4 (CCR4) serves as a receptor for two chemokines: thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). It has been identified as a valuable marker for Type 2 T helper (Th2) cells. According to a recent study published in Modern Rheumatology, elevated levels of CCR4 expression in peripheral blood samples could potentially indicate the effectiveness of abatacept in treating rheumatoid arthritis (RA).
The study conducted by Dr. Tanaka and colleagues involved 30 patients with RA who were undergoing abatacept treatment. Peripheral blood mononuclear cells (PBMCs) were collected from the participants for DNA microarray analysis. After scrutinizing the DNA microarray results, the researchers focused on CCR4 and assessed its expression using flow cytometry in 16 newly diagnosed and treatment-naïve RA patients. The abatacept responders exhibited an increase in CCR4 expression. Notably, the degree of improvement in the clinical disease activity index (CDAI) was significantly correlated with the expression levels of CCR4. CCR4 was predominantly detected in CD4+ T cells within PBMCs, and the proportion of CD4+ T cells expressing CCR4 was significantly higher in RA patients compared to healthy individuals. It’s worth noting that T helper 17 (Th17) and Regulatory T cells (Treg) exhibited higher levels of CCR4 expression than non-Th17-related helper T cells.
Honzawa and colleagues conducted an animal model study to investigate the impact of CCR4 on collagen-induced arthritis (CIA). They observed clusters of CCR4-expressing memory Th17 cells and dendritic cells (DCs) producing CC chemokine ligand 22 (CCL22) in the lymph nodes (LNs) of CIA mice. This observation suggested that the CCR4-CCL22 axis plays a role in fostering the expansion of Th17 cells within the LNs. The researchers also noted that the administration of Compound 22, a CCR4 inhibitor, led to an improvement in disease severity. This improvement was attributed to the reduction of Th17 cells not only in the arthritic joints and LNs but also in the Th17-DC clusters present in the LNs. Furthermore, the study noted that mice deficient in CCR4 and belonging to the C57BL/6J background exhibited significant resistance to the induction of CIA when compared to wild-type mice.
The study unveiled a correlation between elevated CCR4 levels and the effectiveness of abatacept in managing RA. Evaluating the efficacy of biological disease-modifying anti-rheumatic drugs (bDMARDs) poses challenges, and the utilization of CCR4 as a fresh biomarker for forecasting treatment efficacy in RA holds considerable promise. However, more extensive studies are necessary to validate and comprehensively grasp the significance of CCR4 within the context of RA.
- Tanaka S, Etori K, Hattori K, Tamura J, Ikeda K, Kageyama T, et al. CCR4 predicts the efficacy of abatacept in rheumatoid arthritis patients through the estimation of Th17 and Treg cell abundance. Mod Rheumatol. 2023 Jul 31;road077.
- Honzawa T, Matsuo K, Hosokawa S, Kamimura M, Kaibori Y, Hara Y, et al. CCR4 plays a pivotal role in Th17 cell recruitment and expansion in a mouse model of rheumatoid arthritis. Int Immunol. 2022 Dec 31;34(12):635–42.
- Andrew DP, Ruffing N, Kim CH, Miao W, Heath H, Li Y, et al. C-C Chemokine Receptor 4 Expression Defines a Major Subset of Circulating Nonintestinal Memory T Cells of Both Th1 and Th2 Potential. The Journal of Immunology. 2001 Jan 1;166(1):103–11.