Abstract: TH-PO543
CD39 Expression Is Significantly Upregulated in Polarized Macrophage in ANCA Associated Vasculitis Patients
Session Information
- Pathology and Lab Medicine
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1700 Pathology and Lab Medicine
Authors
- Yard, Benito, Ruprecht Karls Universitat Heidelberg, Mannheim, Baden-Württemberg, Germany
- Kälsch, Anna-Isabelle, Ruprecht Karls Universitat Heidelberg, Mannheim, Baden-Württemberg, Germany
Background
Monocytes concurrently stimulated for 6 days with CSF1 and of IFNγ followed by TLR4 activation, are poorly stimulating T-cell proliferation despite increased expression of co-stimulatory molecules. Substitution of IFNγ for IL-4 increases the ability to stimulate T-cell proliferation. These concurrently stimulated (CS) macrophages are tentatively referred as CSM1 and CSM2 respectively. We assessed if CSM1 and CSM2 macrophages from active, therapy naïve, ANCA associated vasculitis (AAV) patients (MPA: n=4 GPA: n=7) differ in phenotype and function from healthy controls (HC, n=12).
Methods
Phenotype and function were assessed by FACS and allogeneic mixed leucocyte reaction (MLC) respectively.
Results
Our study reveals that: 1) AAV patients had significantly more monocytes in peripheral blood as compared to HC. 2) both CD39 and CD73 expression were significantly higher in CSM1 than inCSM2 Macrophages, both in AAV patients and HC. However, surface expression of CD39 on CSM1 macrophages in AAV patients was significantly higher than in HC. 3) IL-17 production in MLC was higher for CSM1 as compared to CSM2 macrophages and blunted by addition of adenosine deaminase. No differences between AAV patients and HC were found. 4) Addition of the pan adenosine receptor NECA to anti-CD3 stimulated T-cells increased IL-17 production and resulted in T-cells with a non-pathogenic Th17 phenotype that were able to suppress proliferation of mitogen activate T-cells.
Conclusion
In keeping that adenosine signalling plays important regulatory roles in immunity, the finding that CD39 on CSM1 macrophages is increased in AAV patient warrants further studies on the functionality of these cells.