Why DNase Treatment for Autoimmune Inflammation Fails — And How to Fix It | Research

The takeaway

Cell-free DNA complexed with the antimicrobial peptide LL37 resists DNase degradation and drives inflammation; stripping these immune complexes is essential for effective DNase therapy.

DNA-LL37 complexes block therapy
Immune complexes resist DNase and amplify inflammation in autoimmune disease

What the researchers found

cfDNA-LL37 immune complexes resist DNase degradation and amplify inflammation; disrupting these complexes before DNase treatment is required for effective inflammation control.

Why it matters

DNase therapy has shown promise for autoimmune diseases but often fails in practice. Understanding that LL37-DNA complexes block its action reveals why — and how to make it work.

How the study worked

Laboratory study examining cfDNA-LL37 immune complex formation, DNase resistance mechanisms, and strategies to improve DNase therapeutic efficacy.

What this study cannot tell us

In vitro study — in vivo complex disruption strategies need validation; multiple antimicrobial peptides beyond LL37 may form similar complexes.

How to read the evidence

Mechanistic laboratory study — reveals important therapeutic obstacle with clear implications for drug development.

When this study was published

Published in 2026, advancing understanding of why DNase therapy underperforms in autoimmune conditions.

The bigger picture

This explains a major barrier in autoimmune therapy and connects antimicrobial peptide biology to autoimmune disease — LL37, normally protective against infections, becomes harmful when it complexes with self-DNA.

Questions still open

Could LL37-targeting antibodies be used alongside DNase to treat autoimmune diseases?
Do LL37-cfDNA complexes serve as biomarkers for autoimmune disease severity?

Common questions

What is LL37 and why does it matter in autoimmune disease?

LL37 is an antimicrobial peptide our body makes to fight infections. But in autoimmune diseases, it binds to self-DNA released from dying cells, creating complexes that resist degradation and trigger excessive immune responses.

Could this lead to better treatments for lupus?

Yes — understanding that LL37-DNA complexes block DNase therapy suggests new approaches: first disrupt these complexes, then use DNase to clear the DNA. This two-step strategy could make DNase therapy effective for lupus and similar conditions.

Read the original research

Stripping cell-free DNA from its immune complex is essential for inflammation control using DNase I.

Biomaterials, 329, 123992

View on PubMed ↗Publisher’s paper ↗

Citation

Chen, Shi; Du, Yibo; Zhu, Chenxu; Li, Chuang; Liu, Xingliang; Liu, Lixin; Chen, Yongming. (2026). Stripping cell-free DNA from its immune complex is essential for inflammation control using DNase I.. Biomaterials, 329, 123992. https://doi.org/10.1016/j.biomaterials.2026.123992