CCR6+ Th cell populations distinguish ACPA positive from ACPA negative rheumatoid arthritis

Paulissen, Sandra M. J.; Hamburg, Jan Piet van; Davelaar, Nadine; Vroman, Heleen; Hazes, Johanna M. W.; Jong, Pascal H P de; Lubberts, Erik

doi:10.1186/s13075-015-0800-5

Cited by 40 publications

(37 citation statements)

References 57 publications

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“…Furthermore, we observed CXCR3 + CCR4 + (double positive, DP) and CXCR3 - CCR4 - (double negative, DN) CCR6 + T EM cells. Although little is known about the function of these cells, it has been described that the DP CCR6 + T EM cells produce low levels of IL-17A and RORC with intermediate IFN-γ and T-bet levels [28]. In our study, we did not observe differences in these unclassified DP and DN population of either CCR6 + or CCR6 - CD4 + T EM cells between r-GPA patients and HCs (data not shown).…”

Section: Resultscontrasting

confidence: 49%

Chemokine receptor co-expression reveals aberrantly distributed TH effector memory cells in GPA patients

et al. 2017

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BackgroundPersistent expansion of circulating CD4+ effector memory T cells (TEM) in patients with granulomatosis with polyangiitis (GPA) suggests their fundamental role in disease pathogenesis. Recent studies have shown that distinct functional CD4+ TEM cell subsets can be identified based on expression patterns of chemokine receptors. The current study aimed to determine different CD4+ TEM cell subsets based on chemokine receptor expression in peripheral blood of GPA patients. Identification of particular circulating CD4+ TEM cells subsets may reveal distinct contributions of specific CD4+ TEM subsets to the disease pathogenesis in GPA.MethodPeripheral blood of 63 GPA patients in remission and 42 age- and sex-matched healthy controls was stained immediately after blood withdrawal with fluorochrome-conjugated antibodies for cell surface markers (CD3, CD4, CD45RO) and chemokine receptors (CCR4, CCR6, CCR7, CRTh2, CXCR3) followed by flow cytometry analysis. CD4+ TEM memory cells (CD3+CD4+CD45RO+CCR7-) were gated, and the expression patterns of chemokine receptors CXCR3+CCR4-CCR6-CRTh2-, CXCR3-CCR4+CCR6-CRTh2+, CXCR3-CCR4+CCR6+CRTh2-, and CXCR3+CCR4-CCR6+CRTh2- were used to distinguish TEM1, TEM2, TEM17, and TEM17.1 cells, respectively.ResultsThe percentage of CD4+ TEM cells was significantly increased in GPA patients in remission compared to HCs. Chemokine receptor co-expression analysis within the CD4+ TEM cell population demonstrated a significant increase in the proportion of TEM17 cells with a concomitant significant decrease in the TEM1 cells in GPA patients compared to HC. The percentage of TEM17 cells correlated negatively with TEM1 cells in GPA patients. Moreover, the circulating proportion of TEM17 cells showed a positive correlation with the number of organs involved and an association with the tendency to relapse in GPA patients. Interestingly, the aberrant distribution of TEM1 and TEM17 cells is modulated in CMV- seropositive GPA patients.ConclusionsOur data demonstrates the identification of different CD4+ TEM cell subsets in peripheral blood of GPA patients based on chemokine receptor co-expression analysis. The aberrant balance between TEM1 and TEM17 cells in remission GPA patients, showed to be associated with disease pathogenesis in relation to organ involvement, and tendency to relapse.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1343-8) contains supplementary material, which is available to authorized users.

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Section: Resultscontrasting

confidence: 49%

Chemokine receptor co-expression reveals aberrantly distributed TH effector memory cells in GPA patients

et al. 2017

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“…In addition, higher proportions of CCR6 + T cells within peripheral blood mononuclear cells were observed in RA patients with anti‐citrullinated antibodies (ACPAs). CCR6 + cells were inversely correlated with disease duration in ACPA‐RA patients . These data highlight the importance of CCR6 as part of the adaptive immune system to develop arthritis.…”

Section: Discussionmentioning

confidence: 63%

CCR6 controls autoimmune but not innate immunity‐driven experimental arthritis

Bonelli

Puchner

Göschl

et al. 2018

J Cellular Molecular Medi

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, characterized by synovial infiltration of various inflammatory cells. Chemokines are involved in controlling the recruitment of different cell types into the synovial membrane. The role of CCR6 in the development of arthritis so far remains unclear. In this study, we investigated the role of CCR6 in the pathogenesis of arthritis using three different murine arthritis models. Compared to WT animals, CCR6 −/− mice developed less clinical signs of arthritis in the collagen‐induced arthritis model but not in the K/BxN serum transfer arthritis model and in the human tumour necrosis factor transgenic arthritis model, suggesting a defect in adaptive effector functions but intact innate effector functions in the development of arthritis in CCR6 −/− animals. In line with this, anti‐collagen antibody levels were significantly reduced in CCR6 −/− mice compared with WT mice. Moreover, we demonstrate enhanced osteoclastogenesis in vitro in CCR6 −/− mice compared with WT mice. However, we did not detect differences in bone mass under steady state conditions in vivo between WT and CCR6‐deficient mice. These data suggest that CCR6 is crucially involved in adaptive but not in innate immunity‐driven arthritis. CCR6 or its chemokine ligand CCL20 might represent a possible new target for the treatment of RA.

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“…As Th17.1 cells are primarily thought to be progeny of Th17 cells [8][9][10][11][12][13][14][15], we aimed to quantify Th1, Th2 and all CCR6 + Th subpopulations in sarcoidosis BALF (n=36), sarcoidosis MLNs (n=17) and control MLNs (n=22) (for gating strategy, see supplementary figure E3). The CCR6 + double-positive cells are thought to reflect an intermediate stage between Th17 and Th17.1 cells [16][17][18].…”

Section: Resultsmentioning

confidence: 99%

Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes

et al. 2018

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The lung-draining mediastinal lymph nodes (MLNs) are currently widely used to diagnose sarcoidosis. We previously reported that T-helper (Th) 17.1 cells are responsible for the exaggerated interferon-γ production in sarcoidosis lungs. In this study, we aimed to investigate 1) whether Th17.1 cells are also increased in the MLNs of sarcoidosis patients and 2) whether frequencies of the Th17.1 cells at diagnosis may correlate with disease progression.MLN cells from treatment-naive pulmonary sarcoidosis patients (n=17) and healthy controls (n=22) and peripheral blood mononuclear cells (n=34) and bronchoalveolar lavage fluid (BALF) (n=36) from sarcoidosis patients were examined for CD4 T-cell subset proportions using flow cytometry.Higher proportions of Th17.1 cells were detected in sarcoidosis MLNs than in control MLNs. Higher Th17.1 cell proportions were found in sarcoidosis BALF compared with MLNs and peripheral blood. Furthermore, BALF Th17.1 cell proportions were significantly higher in patients developing chronic disease than in patients undergoing resolution within 2 years of clinical follow-up.These data suggest that Th17.1 cell proportions in pulmonary sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical practice and could serve as a new therapeutic target.

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CCR6+ Th cell populations distinguish ACPA positive from ACPA negative rheumatoid arthritis

Cited by 40 publications

References 57 publications

Chemokine receptor co-expression reveals aberrantly distributed TH effector memory cells in GPA patients

Chemokine receptor co-expression reveals aberrantly distributed TH effector memory cells in GPA patients

CCR6 controls autoimmune but not innate immunity‐driven experimental arthritis

Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes

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