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Research article
Isao Matsumoto
University of Tsukuba: Tsukuba Daigaku
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Objective:
Aberrant autoantibody production is characteristic of systemic lupus erythematosus (SLE) but follicular regulatory T (TFR) cells potentially can suppress this abnormality. Here, we investigate functional changes in TFR cells from SLE patients.
Methods:
Circulating TFR cells were collected from 19 SLE patients and 14 healthy controls to compare molecular expression and in vitro suppressive capacity of follicular helper T (TFH) cell proliferation. We then tested IL-2 in SLE-TFR cells to check restoration of suppressor function.
Results:
Programmed death-1 (PD-1) expression in SLE-TFR cells was positively correlated with anti-DNA antibody levels and disease activity. These cells had impaired suppressive function for TFH cells with decreased expression of suppression mediators forkhead box p3 (Foxp3), cytotoxic T-lymphocyte antigen 4 (CTLA4), and IL-2 receptor alpha (IL2Rα). In vitro IL-2 stimulation restored expression of these molecules.
Conclusion:
SLE-TFR cells have functional TFH suppression defects but low-dose IL-2 therapy could be useful to restore this ability.
Keywords
Systemic lupus erythematosus, PD-1, T follicular regulatory cell
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
- SLEARTmethods.docx
- suppl1.tif
Representative image of TFR cells used for fluoresceine activated cell sorting. CXCR5: C-X-C chemokine receptor 5.
- suppl2.tif
Suppression assay with PD-1hi TFR cells from HCs.
- supplTable1.tif
Characteristics of SLE patients enrolled in the study. Patient 11, 17, 18 were treatment-naïve at the time of sample collection. Means and standard deviations for age, prednisolone dose, anti-DNA antibody titers, and SLEDAI-2k are given in the bottom row. SLEDAI-2k: systemic lupus erythematosus disease activity index-2k, HCQ: hydroxychloroquine, TAC: tacrolimus, MMF: mycophenolate mofetil, BEL: belimumab, AZA: azathioprine, CsA: ciclosporin A, CY: cyclophosphamide hydrate.
- supplTable2.tif
Comparison of clinical features of patients with SLE and healthy controls (HCs). Values presented as mean ± standard deviations. SLEDAI-2k: systemic lupus erythematosus disease activity index-2k.
- supplTable3.tif
Antibodies used for flow cytometric analysis. All antibodies were used with appropriate isotype controls. CCR: C-C chemokine receptor, CTLA4: cytotoxic T-lymphocyte antigen 4, CXCR: C-X-C chemokine receptor, Foxp3: forkhead box p3, GITR: glucocorticoid-induced TNF receptor, PD-1: programmed death-1, PerCP: peridinin-chlorophyll-protein, Cy: cyanine, PE: phycoerythrin, APC: allophycocyanin.
- supplTable4.tif
Primers used for pyrosequencing.
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research article
Isao Matsumoto
University of Tsukuba: Tsukuba Daigaku
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Clinical & Experimental Immunology.
Version 1
Posted 15 Mar, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Clinical & Experimental Immunology.
Objective:
Aberrant autoantibody production is characteristic of systemic lupus erythematosus (SLE) but follicular regulatory T (TFR) cells potentially can suppress this abnormality. Here, we investigate functional changes in TFR cells from SLE patients.
Methods:
Circulating TFR cells were collected from 19 SLE patients and 14 healthy controls to compare molecular expression and in vitro suppressive capacity of follicular helper T (TFH) cell proliferation. We then tested IL-2 in SLE-TFR cells to check restoration of suppressor function.
Results:
Programmed death-1 (PD-1) expression in SLE-TFR cells was positively correlated with anti-DNA antibody levels and disease activity. These cells had impaired suppressive function for TFH cells with decreased expression of suppression mediators forkhead box p3 (Foxp3), cytotoxic T-lymphocyte antigen 4 (CTLA4), and IL-2 receptor alpha (IL2Rα). In vitro IL-2 stimulation restored expression of these molecules.
Conclusion:
SLE-TFR cells have functional TFH suppression defects but low-dose IL-2 therapy could be useful to restore this ability.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
- SLEARTmethods.docx
- suppl1.tif
Representative image of TFR cells used for fluoresceine activated cell sorting. CXCR5: C-X-C chemokine receptor 5.
- suppl2.tif
Suppression assay with PD-1hi TFR cells from HCs.
- supplTable1.tif
Characteristics of SLE patients enrolled in the study. Patient 11, 17, 18 were treatment-naïve at the time of sample collection. Means and standard deviations for age, prednisolone dose, anti-DNA antibody titers, and SLEDAI-2k are given in the bottom row. SLEDAI-2k: systemic lupus erythematosus disease activity index-2k, HCQ: hydroxychloroquine, TAC: tacrolimus, MMF: mycophenolate mofetil, BEL: belimumab, AZA: azathioprine, CsA: ciclosporin A, CY: cyclophosphamide hydrate.
- supplTable2.tif
Comparison of clinical features of patients with SLE and healthy controls (HCs). Values presented as mean ± standard deviations. SLEDAI-2k: systemic lupus erythematosus disease activity index-2k.
- supplTable3.tif
Antibodies used for flow cytometric analysis. All antibodies were used with appropriate isotype controls. CCR: C-C chemokine receptor, CTLA4: cytotoxic T-lymphocyte antigen 4, CXCR: C-X-C chemokine receptor, Foxp3: forkhead box p3, GITR: glucocorticoid-induced TNF receptor, PD-1: programmed death-1, PerCP: peridinin-chlorophyll-protein, Cy: cyanine, PE: phycoerythrin, APC: allophycocyanin.
- supplTable4.tif
Primers used for pyrosequencing.
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