Therapeutic single-cell landscape: methotrexate exacerbates interstitial lung disease by compromising the stemness of alveolar epithelial cells under systemic inflammation.

ABSTRACT:

Background

Interstitial lung disease (ILD) poses a serious threat in patients with rheumatoid arthritis (RA). However, the impact of cornerstone drugs, including methotrexate (MTX) and TNF inhibitor, on RA-associated ILD (RA-ILD) remains controversial.

Methods

Using an SKG mouse model and single-cell transcriptomics, we investigated the effects of MTX and TNF blockade on ILD.

Findings

Our study revealed that MTX exacerbates pulmonary inflammation by promoting immune cell infiltration, Th17 activation, and fibrosis. In contrast, TNF inhibitor ameliorates these features and inhibits ILD progression. Analysis of data from a human RA-ILD cohort revealed that patients with ILD progression had persistently higher systemic inflammation than those without progression, particu

SUBMITTER: Chang SH 

PROVIDER: S-EPMC11437874 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature