| First Author | Chan TY | Year | 2019 |
| Journal | Eur J Immunol | Volume | 49 |
| Issue | 11 | Pages | 2063-2073 |
| PubMed ID | 31350760 | Mgi Jnum | J:281748 |
| Mgi Id | MGI:6379488 | Doi | 10.1002/eji.201948141 |
| Citation | Chan TY, et al. (2019) Increased ILC3s associated with higher levels of IL-1beta aggravates inflammatory arthritis in mice lacking phagocytic NADPH oxidase. Eur J Immunol 49(11):2063-2073 |
| abstractText | 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-1beta on Tbet(+) ILC1s from joints facilitated their differentiation into ROR-gammat(+) 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-1beta 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. |
