ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
This article is part of the Research TopicImmune Cell Dynamics in Pulmonary Fibrosis: From Mechanisms to Therapeutic TargetsView all articles
Nerandomilast attenuates idiopathic inflammatory myopathy-associated interstitial lung disease via inhibiting proliferation and differentiation of B cells
Provisionally accepted
Yuming Liu1
Yayue Hu1,2
rigeleng Se1Zhongyi Yang1Xueze Liu1Jiayang Yu1,2Huihui Li1,2Songtao Gu3Weitao Yang4
Cheng Yang1,2
Honggang Zhou1,2Yujie He5*Chunyu Kong1*
Xiaoting Gu1,2*
Xiaohe Li1,2*- 1Nankai University State Key Laboratory of Medicinal Chemical Biology, Tianjin, China
- 2Tianjin International Joint Academy of Biomedicine, Tianjin, China
- 3Tianjin Chest Hospital, Tianjin, China
- 4Xuchang Central Hospital, Xuchang, China
- 5The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract: Idiopathic Inflammatory Myopathy-associated Interstitial Lung Disease (IIM-ILD) is an autoimmune disorder with unsatisfactory treatment outcomes. Phosphodiesterase 4B (PDE4B) is a key enzyme in the metabolism of cyclic adenosine monophosphate (cAMP) in lung tissue, and targeting PDE4B has been proposed as a promising therapeutic strategy. Here, we evaluate Nerandomilast, a PDE4B inhibitor, for the management of IIM-ILD. In the animal model, Nerandomilast ameliorated muscle inflammation, pulmonary fibrosis, and pulmonary inflammation. Mechanism studies demonstrate that Nerandomilast significantly suppresses PDE4B expression while elevating cAMP levels within B cells of lung tissue. This regulatory effect was further validated through multidimensional experiments: immunohistochemistry confirmed reduced CD19⁺ B cell infiltration; Western blot and immunofluorescence revealed downregulated expression of plasma cell marker CD138; qRT-PCR analysis showed suppressed mRNA expression of key plasma cell differentiation transcription factors; serological testing indicated a significant decrease in anti-Jo-1 autoantibody positivity. Signal pathway analysis revealed that Nerandomilast co-inhibits phosphorylation activation of PI3K/AKT, NF-κB, and STAT3 pathways in B cells via the cAMP/PKA axis, while simultaneously enhancing CREB signaling activity, thereby reconstructing B cell immune homeostasis at both transcriptional and functional levels. This study is the first to establish that Nerandomilast alleviates IIM-ILD via cAMP-mediated B cell reprogramming. Future research will further validate its long-term efficacy in more complex models resembling human diseases and explore deeper mechanisms of its involvement in B-cell regulation to accelerate its translation into clinical applications.
Keywords: B cells, cAMP, IIM-ILD, Nerandomilast, PDE4B
Received: 18 Dec 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Liu, Hu, Se, Yang, Liu, Yu, Li, Gu, Yang, Yang, Zhou, He, Kong, Gu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yujie He
Chunyu Kong
Xiaoting Gu
Xiaohe Li
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.