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Dendritic cell integrin expression patterns regulate inflammation in the rheumatoid arthritis joint

Lookup NU author(s): Leonie Schittenhelm, Dr Arthur Pratt, Dr Catharien Hilkens

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

Objectives: Immune dysregulation contributes to the development of RA. Altered surface expression patterns of integrin adhesion receptors by immune cells is one mechanism by which this may occur. We investigated the role of β2 integrin subunits CD11a and CD11b in dendritic cell (DC) subsets of RA patients.Methods: Total β2 integrin subunit expression and its conformation ('active' vs 'inactive' state) were quantified in DC subsets from peripheral blood (PB) and SF of RA patients as well as PB from healthy controls. Ex vivo stimulation of PB DC subsets and in vitro-generated mature and tolerogenic monocyte-derived DCs (moDCs) were utilized to model the clinical findings. Integrin subunit contribution to DC function was tested by analysing clustering and adhesion, and in co-cultures to assess T cell activation.Results: A significant reduction in total and active CD11a expression in DCs in RA SF compared with PB and, conversely, a significant increase in CD11b expression was found. These findings were modelled in vitro using moDCs: tolerogenic moDCs showed higher expression of active CD11a and reduced levels of active CD11b compared with mature moDCs. Finally, blockade of CD11b impaired T cell activation in DC-T cell co-cultures.Conclusion: For the first time in RA, we show opposing expression of CD11a and CD11b in DCs in environments of inflammation (CD11alow/CD11bhigh) and steady state/tolerance (CD11ahigh/CD11blow), as well as a T cell stimulatory role for CD11b. These findings highlight DC integrins as potential novel targets for intervention in RA.


Publication metadata

Author(s): Schittenhelm L, Roberston J, Pratt AG, Hilkens CM, Morrison VL

Publication type: Article

Publication status: Published

Journal: Rheumatology

Year: 2020

Issue: ePub ahead of Print

Online publication date: 30/10/2020

Acceptance date: 07/09/2020

Date deposited: 11/11/2020

ISSN (print): 0080-2727

ISSN (electronic): 1662-3959

Publisher: S. Karger AG

URL: https://doi.org/10.1093/rheumatology/keaa686

DOI: 10.1093/rheumatology/keaa686

PubMed id: 33123735


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