| First Author | Wu EK | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 11 | Pages | 2837-2849 |
| PubMed ID | 31659014 | Mgi Jnum | J:282190 |
| Mgi Id | MGI:6379886 | Doi | 10.4049/jimmunol.1900473 |
| Citation | Wu EK, et al. (2019) TNF-Induced Interstitial Lung Disease in a Murine Arthritis Model: Accumulation of Activated Monocytes, Conventional Dendritic Cells, and CD21(+)/CD23(-) B Cell Follicles Is Prevented with Anti-TNF Therapy. J Immunol 203(11):2837-2849 |
| abstractText | Interstitial lung disease (ILD) is a well-known extra-articular manifestation of rheumatoid arthritis (RA). RA-associated ILD (RA-ILD) exists on a wide spectrum, with variable levels of inflammatory and fibrotic activity, although all subtypes are regarded as irreversible pathologic conditions. In both articular and pulmonary manifestations, TNF is a significant pathogenic factor. Whereas anti-TNF therapy alleviates joint pathologic conditions, it exacerbates fibrotic RA-ILD. The TNF-transgenic (TNF-Tg) murine model of RA develops both inflammatory arthritis and an ILD that mimics a cellular nonspecific interstitial pneumonia pattern dominated by an interstitial accumulation of inflammatory cells with minimal-to-absent fibrosis. Given the model's potential to elucidate the genesis of inflammatory RA-ILD, we aim to achieve the following: 1) characterize the cellular accumulations in TNF-Tg lungs, and 2) assess the reversibility of inflammatory ILD following anti-TNF therapy known to resolve TNF-Tg inflammatory arthritis. TNF-Tg mice with established disease were randomized to anti-TNF or placebo therapy and evaluated with imaging, histology, and flow cytometric analyses, together with wild-type controls. Flow cytometry of TNF-Tg versus wild-type lungs revealed significant increases in activated monocytes, conventional dendritic cells, and CD21(+)/CD23(-) B cells that are phenotypically distinct from the B cells in inflamed nodes, which are known to accumulate in joint-draining lymph nodes. In contrast to human RA-ILD, anti-TNF treatment significantly alleviated both joint and lung inflammation. These results identify a potential role for activated monocytes, conventional dendritic cells, and CD21(+)/CD23(-) B cells in the genesis of RA-ILD, which exist in a previously unknown, reversible, prefibrotic stage of the disease. |
