Opin vísindi

Mapping of Signaling Pathways Linked to sIgAD Reveals Impaired IL-21 Driven STAT3 B-Cell Activation

Show simple item record

dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Lemarquis, Andri Leo
dc.contributor.author Theodors, Fannar
dc.contributor.author Einarsdottir, Helga K.
dc.contributor.author Ludviksson, Bjorn
dc.date.accessioned 2020-10-08T11:52:23Z
dc.date.available 2020-10-08T11:52:23Z
dc.date.issued 2019-03-18
dc.identifier.citation Lemarquis AL, Theodors F, Einarsdottir HK and Ludviksson BR (2019) Mapping of Signaling Pathways Linked to sIgAD Reveals Impaired IL-21 Driven STAT3 B-Cell Activation. Front. Immunol. 10:403. doi: 10.3389/fimmu.2019.00403
dc.identifier.issn 1664-3224
dc.identifier.uri https://hdl.handle.net/20.500.11815/2102
dc.description Publisher's version (útgefin grein)
dc.description.abstract Objectives: It has recently been shown that individuals with selective IgA deficiency (sIgAD) have defective B cell responses both to T cell dependent and independent mimicking stimulations. The complex intracellular signaling pathways from different stimuli leading to IgA isotype switching have not been fully elucidated. Thus, the main objective of this study was to delineate these pathways and their potential role in the immunopathology linked to sIgAD. Materials and Methods: PBMCs from 10 individuals with sIgAD and 10 healthy controls (HC) were activated in vitro via either a T cell dependent or independent mimicking stimulation. Intracellular phosphorylation of pSTAT3, pSTAT5, pSTAT6, and as pERK1/2 was evaluated in T and B cells using phosphoflow cytometry. Results: By evaluating T cell dependent cytokine driven pathways linked to IgA isotype induction we identified a defect involving an IL-21 driven STAT3 activation isolated to B cells in sIgAD individuals. However, all other signaling pathways studied were found to be normal compared to HC. In T cell dependent cytokine driven stimulations linked to IgA isotype induction the following patterns emerged: (i) IL-10 led to significant STAT3 activation in both T- and B cells; (ii) IL-4 stimulation was predominantly confined to STAT6 activation in both T- and B cells, with some effects on STAT3 activation in T-cells; (iii) as expected, of tested stimuli, IL-2 alone activated STAT5 and some STAT3 activation though in both cases only in T-cells; (iv) IL-21 induced significant activation of STAT3 in both T- and B cells, with some effects on STAT5 activation in T-cells; and finally (v) synergistic effects were noted of IL-4+IL-10 on STAT5 activation in T-cells, and possibly STAT6 in both T- and B cells. On the other hand, CPG induced T cell independent activation was confined to ERK1/2 activation in B cells. Conclusion: Our results indicate a diminished STAT3 phosphorylation following IL-21 stimulation solely in B cells from sIgAD individuals. This can represent aberrant germinal center reactions or developmental halt. Thus, our work provides further insight into the unraveling of the previously hypothesized role of IL-21 to reconstitute immunoglobulin production in primary antibody deficiencies.
dc.description.sponsorship We are grateful to the patients of this study and to the staff and the Icelandic Medical Research Center for blood sample collection and assistance with the patients. We thank the funding partners: The Icelandic Research Fund and The University hospital of Iceland research fund.
dc.format.extent 403
dc.language.iso en
dc.publisher Frontiers Media SA
dc.relation.ispartofseries Frontiers in Immunology;10(MAR)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Selective IgA deficiency
dc.subject IL-21
dc.subject pSTAT3
dc.subject Phosphoflow
dc.subject B cells
dc.subject T cells
dc.subject IgA
dc.subject Ónæmisfræði
dc.title Mapping of Signaling Pathways Linked to sIgAD Reveals Impaired IL-21 Driven STAT3 B-Cell Activation
dc.type info:eu-repo/semantics/article
dcterms.license This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.description.version Peer Reviewed
dc.identifier.journal Frontiers in Immunology
dc.identifier.doi 10.3389/fimmu.2019.00403
dc.relation.url https://www.frontiersin.org/article/10.3389/fimmu.2019.00403/full
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

Files in this item

This item appears in the following Collection(s)

Show simple item record