Session Title: Vasculitis
Session Type: Abstract Submissions (ACR)
Human FoxP3+T-cells are functionally heterogeneous, and can be classified into three phenotypically distinct subpopulations based on the expression levels of FoxP3 and the memory T-cell marker CD45RO. These three subpopulations can be defined as: activated suppressor TRegs (FoxP3HighCD45RO+; ASTReg), resting suppressor TRegs (FoxP3LowCD45RO–; RSTReg), and cytokine-secreting non-suppressor TRegs (FoxP3LowCD45RO+; NONTReg).
This study aimed to evaluate the identity of the elevated frequency of FoxP3+T-cells in patients with granulomatosis with polyangiitis (GPA).
Peripheral blood mononuclear cells were isolated from 46 GPA-patients (27 ANCA-positief and 19 ANCA-negative at the time of inclusion) in remission and from 22 age- and sex-matched HCs. Expression of CD4, CD45RO, and FoxP3 was determined by flow cytometric analysis. The expression levels of FoxP3 and CD45RO were used for distinction between ASTReg , RSTReg, and NONTReg FoxP3+T-cells. Next, frequencies of intracellular production of IL-17 within the FoxP3+ cell subpopulations were analyzed by flow cytometry in peripheral blood of ANCA-positive (n=10) and ANCA-negatieve (n=9) GPA-patients and matched HCs (n=12) upon ex vivo stimulation with phorbol-myristate-acetate and calcium ionophore in the presence of brefeldin A.
A significant increase in the frequency of FoxP3+TReg cells was observed in GPA-patients as compared with HCs. No differences were detected in RSTReg– and ASTReg cells between GPA-patients and HCs, whereas the NONTReg cells were significantly increased in GPA-patients. The distribution of RSTReg– and NONTReg cells did not differ between ANCA-negative and ANCA-positive patients, whereas lower percentages of ASTReg cells were observed in ANCA-positive patients as compared to ANCA-negative patients and HCs. In addition, frequencies of IL-17+ T-cells were significantly increased within the NONTReg subset from ANCA-positive patients in comparison with ANCA-negative patients and HCs, whereas no such difference was found between ANCA-negative patients and HCs.
Conclusion: Increased FoxP3 expression in CD4+T-cells from GPA-patients is related to an increase in a subset of non-suppressive T-cells that produce higher levels of IL-17 and display low expression of FoxP3. Plasticity of CD4+T-cells in GPA points towards FoxP3+IL-17+ effector cells and decrease in suppressive TReg cells in relation to ANCA production.
W. H. Abdulahad,
C. A. Stegeman,
M. G. Huitema,
P. C. Limburg,
C. G. M. Kallenberg,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-circulating-foxp3-t-cells-in-patients-with-granulomatosis-with-polyangiitis-are-attributed-to-an-increase-in-the-non-suppressor-foxp3low-cd45ro-treg-cell-subpopulation/