Increased ILC3s associated with higher levels of IL-1β aggravates inflammatory arthritis in mice lacking phagocytic NADPH oxidase.

Abstract:

:The role of redox regulation in immune-mediated arthritis has been previously described. However, the relationship between innate immune cells, including innate lymphoid cells (ILCs) and phagocyte-derived ROS, in this process remains unclear. Here, we characterize ILCs and measure the IL-1 family cytokines along with other cytokines relevant to ILC functions and development in serum-induced arthritic joints in wild type and phagocytic NADPH oxidase (NOX2)-deficient Ncf1-/- mice. We found more severe serum-induced joint inflammation and increased NCR+ ILC3s in inflamed joints of Ncf1-/- mice. Furthermore, in vitro stimulation with IL-1β on Tbet+ ILC1s from joints facilitated their differentiation into ROR-γt+ ILC3s. Moreover, treatment with IL-1 antagonists effectively lowered the proportions of NCR+ ILC3s and IL-17A producing ILC3s in Ncf1-/- arthritic mice and ameliorated the joint inflammation. These results suggest that NOX2 is an essential regulator of ILC transdifferentiation and may mediate this process in a redox-dependent manner through IL-1β production in the inflammatory joint. Our findings shed important light on the role of ILCs in the initiation and progression in tissue inflammation and delineate a novel innate immune cell-mediated pathogenic mechanism through which redox regulation may determine the direction of immune responses in joints.

journal_name

Eur J Immunol

authors

Chan TY,Yen CL,Huang YF,Lo PC,Nigrovic PA,Cheng CY,Wang WZ,Wu SY,Shieh CC

doi

10.1002/eji.201948141

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

2063-2073

issue

11

eissn

0014-2980

issn

1521-4141

journal_volume

49

pub_type

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