Advancing research in inflammatory disease and fibrosis

Chronic inflammatory diseases such as inflammatory bowel disease (IBD), Crohn’s disease, and fibrosis remain major clinical challenges, driven by complex interactions within the immune system. A growing focus in this space is the role of innate lymphoid cells (ILCs) that are key regulators of tissue homeostasis and inflammation, particularly in mucosal tissues like the gut.

Understanding how specific ILC subsets contribute to disease has historically been limited by a lack of precise genetic tools. Recent advances in engineered mouse models are now enabling researchers to dissect these pathways with unprecedented specificity.

Cutting-edge research into ILC biology

Professor Kelly McNagny is a leading immunologist at the University of British Columbia (UBC), with research spanning stem cell biology, innate immune responses, inflammation, cancer, and regenerative medicine. Prof. McNagny’s laboratory is internationally recognised for developing transgenic mouse models and disease systems to uncover how immune cells drive pathology and to identify new therapeutic targets

In their recent publication, Prof. McNagny and colleagues address a longstanding gap in the field: the ability to selectively target and study individual ILC subsets in vivo. Their work demonstrates that ILC2s and ILC3s play opposing roles in intestinal inflammation and fibrosis. Loss of ILC2s leads to increased ILC3 activity and heightened fibrosis, while reducing ILC3/Th17 activity protects against fibrotic disease.

These findings reveal a critical immune balance between type 2 and type 3 responses that governs gut homeostasis and disease progression.

A precise and powerful mouse model

Central to this study is the Il17rb-CreERT2-eGFP knock in mouse line, generated by Ozgene. This model was engineered via homologous recombination at the endogenous Il17rb locus without disrupting gene expression, enabling selective targeting of ILC2 cells, tamoxifen-inducible gene deletion for temporal control, and accurate lineage tracing and functional studies in vivo.

This level of precision allowed the researchers to directly demonstrate how ILC2 depletion alters immune balance, driving fibrosis through increased IL-17–producing ILC3 and Th17 responses. Importantly, the study also highlights therapeutic implications: targeting the RORγt pathway in ILC3s can significantly reduce fibrosis, positioning this axis as a promising intervention strategy.

Driving discovery with advanced mouse models

This work shows how customised mouse models can unlock complex biology that would otherwise remain inaccessible. By enabling cell-type–specific targeting, temporal control of gene expression, and physiologically relevant disease modelling, the knock in mouse model played a critical role in uncovering new mechanisms of immune regulation and fibrosis, with clear translational potential for inflammatory diseases.

The collaboration with Professor McNagny’s group highlights the impact of precision genetic models in advancing immunology research. Ozgene is proud to support cutting-edge discoveries like this, where tailored mouse models not only answer fundamental biological questions, but also pave the way for next-generation therapeutic strategies in diseases such as Crohn’s disease and fibrosis.

Mouse models & more information

• For more information on Professor Kelly McNagny’s research into intestinal fibrosis and immune cell interactions, read the publication below or visit his profile at the University of British Columbia: UBC profile
• To learn more about the custom knock-in mouse models for your research, visit our knock-in mouse page or explore Ozgene’s full range of services.

J Exp Med. 2025 Jul 7;222(7):e20241671. doi: 10.1084/jem.20241671.
Functional targeting of ILC2s and ILC3s reveals selective roles in intestinal fibrosis and homeostasis
Ahmed Kabil, Natalia Nayyar, Chengxi Xu, Julyanne Brassard, Lesley A Hill, Samuel B Shin, Sameeksha Chopra, Bernard Lo, Yicong Li, Mya Bal, Marine Theret, Fabio M V Rossi, T Michael Underhill, Michael R Hughes, Kelly M McNagny