γδTCR regulates production of interleukin-27 by neutrophils and attenuates inflammatory arthritis

Scientific Reports
Laura BouchareychasIannis E Adamopoulos

Abstract

γδ T cells have been implicated in inflammatory diseases as an important link between the innate and adaptive immune responses, however, their role in inflammatory arthritis remain unclear. To define the contribution of γδ T cells in the pathogenesis of inflammatory arthritis, we performed gene transfer of IL-23 in B10.RIII mice to establish joint inflammation in the presence or absence of γδ T cells. We demonstrated that γδ T cell blockade has a protective effect on arthritis incidence and severity by preventing neutrophil accumulation in the blood, spleen and bone marrow as well as by reducing neutrophil infiltration into the joints. Furthermore, our data demonstrate that absence of γδ T cells was associated with an increase of IL-27 levels produced by neutrophils and dendritic cells, and systemic IL-27 expression also prevents IL-23-induced inflammatory arthritis and limits neutrophil expansion. Collectively our findings reveal an immunomodulatory effect of γδ T cells on neutrophils associated with IL-27 synthesis and secretion and indicate a novel link between IL-27 and the modulation of γδ T cells and neutrophils that can be targeted in the treatment of inflammatory arthritis.

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Citations

Sep 12, 2019·Seminars in Immunopathology·Cuong Thach NguyenIannis E Adamopoulos
Jan 21, 2020·Immunological Reviews·Charlie BridgewoodDennis McGonagle
Mar 10, 2020·The Journal of Clinical Investigation·Eric GraceyRobert D Inman
May 4, 2020·International Immunopharmacology·Abbas ShahiAliakbar Amirzargar
May 29, 2021·Experimental & Molecular Medicine·Booki MinMatthias J Feige
Aug 27, 2021·Molecular Immunology·Youwen MeiHongbo Qi
Apr 28, 2020·The Journal of Investigative Dermatology·Zhenrui ShiSamuel T Hwang

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Methods Mentioned

BETA
flow cytometry
ELISA
FACS
PCR

Software Mentioned

cellSens Dimension
GraphPad
Chemotaxis and Migration
ImageJ
GraphPad Prism VI
FlowJo

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