# Alpha 1 Antitrypsin Suppresses Autoantibody Production and Cellular Autoimmunity in Chronic Graft-Versus-Host Disease (cGVHD) in a Lupus Mouse Model

## TL;DR

This study shows that alpha-1 antitrypsin reduces autoantibody production and T cell activity in a lupus mouse model, offering new insights for treating lupus.

## Contribution

The study reveals a novel mechanism by which alpha-1 antitrypsin suppresses autoimmunity in a lupus model.

## Key findings

- hAAT significantly blocked anti-dsDNA IgG autoantibody production in lupus mice.
- hAAT inhibited T cell activation, including effector memory and T follicular helper cells.
- hAAT suppressed germinal center formation and function.

## Abstract

Systemic lupus erythematosus (SLE) is a severe autoimmune disease that is challenging to treat due to poor understanding of its pathogenesis and etiology. Clearly understanding and dissecting the therapeutic effects of potential treatment in animal models are important. It has been shown that human alpha-1 antitrypsin (hAAT) holds therapeutic potential for the treatment of autoimmune diseases including lupus. However, the mechanism underlying its protective effect requires further investigation. In the present study, we used a chronic graft-versus-host disease-induced lupus mouse model to test the effect of hAAT on lupus development. We performed adoptive transfer of MHC I-aβ mismatched bm12 splenocytes into hAAT transgenic mice and showed that hAAT significantly blocked the production of anti-dsDNA IgG autoantibodies. Mechanistically, hAAT inhibited T cell activation and proliferation, including that of effector memory T (Tem) and T follicular helper (Tfh) cells. In addition, hAAT suppressed germinal center formation and functions. These results advanced the current understanding of hAAT functions and provide a new insight for the treatment of SLE.