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Regulatory B-cells are reduced in the blood in patients with granulomatosis with polyangiitis, and fail to regulate T-cell IFN-γ production

Appelgren, Daniel ; Puli, Srinivasulu LU ; Hellmark, Thomas LU orcid ; Pochard, Pierre ; Pers, Jacques-Olivier ; Ernerudh, Jan ; Eriksson, Per and Segelmark, Mårten LU (2023) In Clinical and Experimental Immunology 213(2). p.190-201
Abstract

Regulatory B (Breg) cells can dampen inflammation, autoreactivity and transplant rejection. We investigated the frequencies, phenotypes and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and phenotypes of CD24 hiCD27 + and CD24 hiCD38 hi B-cells in the blood were determined with flow cytometry in 37 GPA patients (22 in remission and 15 with active disease) and 31 healthy controls (HC). A co-culture model was used to study the capacity of Breg cells to regulate T-cell activation and proliferation in cells from 10 GPA patients in remission and 12 HC. T-cell cytokine production in... (More)

Regulatory B (Breg) cells can dampen inflammation, autoreactivity and transplant rejection. We investigated the frequencies, phenotypes and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and phenotypes of CD24 hiCD27 + and CD24 hiCD38 hi B-cells in the blood were determined with flow cytometry in 37 GPA patients (22 in remission and 15 with active disease) and 31 healthy controls (HC). A co-culture model was used to study the capacity of Breg cells to regulate T-cell activation and proliferation in cells from 10 GPA patients in remission and 12 HC. T-cell cytokine production in vitro and levels in plasma were determined with ELISA. Frequencies of CD24 hiCD27 + B-cells were reduced both during active disease and remission compared with HC (p=0.005 and p=0.010, respectively), whereas CD24 hiCD38 hi B-cells did not differ. Patient CD24 hiCD27 + B-cells exhibited decreased expression of CD25 but increased expression of PD-L1 and PD-L2 during remission. B-cells from GPA patients regulated T-cell proliferation but failed to regulate IFN-γ production [median T-cells alone 222 ng/ml vs T cells + B-cells 207 ng/ml, p=0.426). IFN-γ were also elevated in patient plasma samples (p=0.016). In conclusion, GPA patients exhibit altered numbers and phenotypes of CD24 hiCD27 + B-cells. This is accompanied by a disability to control T-cell production of Th1-type cytokines during remission, which might be of fundamental importance for the granulomatous inflammation that characterizes the chronic phase of this disease.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical and Experimental Immunology
volume
213
issue
2
pages
190 - 201
publisher
British Society for Immunology
external identifiers
  • scopus:85165521399
  • pmid:36752779
ISSN
0009-9104
DOI
10.1093/cei/uxad021
language
English
LU publication?
yes
id
7e654eb5-b93b-4fcc-a98e-2900cd8106cb
date added to LUP
2023-03-17 11:14:08
date last changed
2024-06-15 01:36:24
@article{7e654eb5-b93b-4fcc-a98e-2900cd8106cb,
  abstract     = {{<p>Regulatory B (Breg) cells can dampen inflammation, autoreactivity and transplant rejection. We investigated the frequencies, phenotypes and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and phenotypes of CD24 hiCD27 + and CD24 hiCD38 hi B-cells in the blood were determined with flow cytometry in 37 GPA patients (22 in remission and 15 with active disease) and 31 healthy controls (HC). A co-culture model was used to study the capacity of Breg cells to regulate T-cell activation and proliferation in cells from 10 GPA patients in remission and 12 HC. T-cell cytokine production in vitro and levels in plasma were determined with ELISA. Frequencies of CD24 hiCD27 + B-cells were reduced both during active disease and remission compared with HC (p=0.005 and p=0.010, respectively), whereas CD24 hiCD38 hi B-cells did not differ. Patient CD24 hiCD27 + B-cells exhibited decreased expression of CD25 but increased expression of PD-L1 and PD-L2 during remission. B-cells from GPA patients regulated T-cell proliferation but failed to regulate IFN-γ production [median T-cells alone 222 ng/ml vs T cells + B-cells 207 ng/ml, p=0.426). IFN-γ were also elevated in patient plasma samples (p=0.016). In conclusion, GPA patients exhibit altered numbers and phenotypes of CD24 hiCD27 + B-cells. This is accompanied by a disability to control T-cell production of Th1-type cytokines during remission, which might be of fundamental importance for the granulomatous inflammation that characterizes the chronic phase of this disease.</p>}},
  author       = {{Appelgren, Daniel and Puli, Srinivasulu and Hellmark, Thomas and Pochard, Pierre and Pers, Jacques-Olivier and Ernerudh, Jan and Eriksson, Per and Segelmark, Mårten}},
  issn         = {{0009-9104}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  pages        = {{190--201}},
  publisher    = {{British Society for Immunology}},
  series       = {{Clinical and Experimental Immunology}},
  title        = {{Regulatory B-cells are reduced in the blood in patients with granulomatosis with polyangiitis, and fail to regulate T-cell IFN-γ production}},
  url          = {{http://dx.doi.org/10.1093/cei/uxad021}},
  doi          = {{10.1093/cei/uxad021}},
  volume       = {{213}},
  year         = {{2023}},
}