TY - JOUR
T1 - Schistosoma mansoni egg-derived thioredoxin and Sm14 drive the development of IL-10 producing regulatory B cells
AU - Chayé, Mathilde A. M.
AU - Gasan, Thomas A.
AU - Ozir-Fazalalikhan, Arifa
AU - Scheenstra, Maaike R.
AU - Zawistowska-Deniziak, Anna
AU - van Hengel, Oscar R. J.
AU - Gentenaar, Max
AU - Manurung, Mikhael D.
AU - Harvey, Michael R.
AU - Codée, Jeroen D. C.
AU - Chiodo, Fabrizio
AU - Heijke, Anouk M.
AU - Kalinowska, Alicja
AU - van Diepen, Angela
AU - Hensbergen, Paul J.
AU - Yazdanbakhsh, Maria
AU - Guigas, Bruno
AU - Hokke, Cornelis H.
AU - Smits, Hermelijn H.
N1 - Funding Information: This work was supported by an AWWA grant from the Lung Foundation Netherlands to H. H. Smits (grant # 12.0.17.001, https://research. longfonds.nl/lung-foundation-netherlands) as well as a ZonMW vidi grant to H.H. Smits (grant # 91714352, https://www.zonmw.nl). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2023 Chayé et al.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing regulatory B (Breg) cells play a signifi-cant role. Schistosoma mansoni soluble egg antigens (SEA) are bound and internalized by B cells and induce both human and mouse IL-10 producing Breg cells. To identify Breg-inducing proteins in SEA, we fractionated SEA by size exclusion chromatography and found 6 fractions able to induce IL-10 production by B cells (out of 18) in the high, medium and low molecular weight (MW) range. The high MW fractions were rich in heavily glycosylated mol-ecules, including multi-fucosylated proteins. Using SEA glycoproteins purified by affinity chromatography and synthetic glycans coupled to gold nanoparticles, we investigated the role of these glycan structures in inducing IL-10 production by B cells. Then, we performed proteomics analysis on active low MW fractions and identified a number of proteins with putative immunomodulatory properties, notably thioredoxin (SmTrx1) and the fatty acid binding protein Sm14. Subsequent splenic murine B cell stimulations and hock immunizations with recombinant SmTrx1 and Sm14 showed their ability to dose-dependently induce IL-10 production by B cells both in vitro and in vivo. Identification of unique Breg cells-induc-ing molecules may pave the way to innovative therapeutic strategies for inflammatory and auto-immune diseases.
AB - During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing regulatory B (Breg) cells play a signifi-cant role. Schistosoma mansoni soluble egg antigens (SEA) are bound and internalized by B cells and induce both human and mouse IL-10 producing Breg cells. To identify Breg-inducing proteins in SEA, we fractionated SEA by size exclusion chromatography and found 6 fractions able to induce IL-10 production by B cells (out of 18) in the high, medium and low molecular weight (MW) range. The high MW fractions were rich in heavily glycosylated mol-ecules, including multi-fucosylated proteins. Using SEA glycoproteins purified by affinity chromatography and synthetic glycans coupled to gold nanoparticles, we investigated the role of these glycan structures in inducing IL-10 production by B cells. Then, we performed proteomics analysis on active low MW fractions and identified a number of proteins with putative immunomodulatory properties, notably thioredoxin (SmTrx1) and the fatty acid binding protein Sm14. Subsequent splenic murine B cell stimulations and hock immunizations with recombinant SmTrx1 and Sm14 showed their ability to dose-dependently induce IL-10 production by B cells both in vitro and in vivo. Identification of unique Breg cells-induc-ing molecules may pave the way to innovative therapeutic strategies for inflammatory and auto-immune diseases.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85164202103&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/37363916
U2 - https://doi.org/10.1371/journal.pntd.0011344
DO - https://doi.org/10.1371/journal.pntd.0011344
M3 - Article
C2 - 37363916
SN - 1935-2727
VL - 17
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 6
M1 - e0011344
ER -