Humans express two forms of TSLP: a long pro-inflammatory cytokine driving atopic diseases, and a short antimicrobial peptide form with anti-inflammatory properties, with tezepelumab approved to target the long form.
2 isoforms, opposite effectsLong TSLP drives inflammation and disease; short TSLP is an antimicrobial peptide that protects barrier tissues
What the researchers found
Human TSLP exists as two functionally distinct isoforms: long-form TSLP acts as a pro-inflammatory cytokine in atopic and neoplastic diseases, while short-form TSLP functions as an anti-inflammatory antimicrobial peptide at barrier surfaces.
Why it matters
Understanding that one gene produces both a disease-driving cytokine and a protective antimicrobial peptide has important implications for therapeutic targeting—ideally blocking the harmful form while preserving the beneficial one.
How the study worked
Narrative review of TSLP biology, focusing on isoform differences, disease associations, SNP effects, and therapeutic targeting with tezepelumab.
What this study cannot tell us
The relative contributions of lfTSLP vs sfTSLP in most diseases are not fully characterized. Whether tezepelumab differentially blocks the two forms is not clear. Most genetic association data are from European populations.
How to read the evidence
Comprehensive review of basic and clinical science. Well-established isoform biology with approved therapeutic (tezepelumab) targeting TSLP.
When this study was published
Published in 2025, providing updated understanding of TSLP biology and therapeutic targeting.
The bigger picture
TSLP exemplifies the dual nature of immune molecules—the same gene product can be protective or pathogenic depending on the form. This has broad implications for immunotherapy design.
Questions still open
- Can therapeutic strategies be developed that selectively block lfTSLP while preserving sfTSLP antimicrobial function?
- Does tezepelumab inadvertently suppress the protective sfTSLP at barrier surfaces?
- Could sfTSLP-based therapeutics be developed as antimicrobial agents?
Common questions
What is TSLP?
Is there a drug that targets TSLP?
Read the original research
Thymic stromal lymphopoietin (TSLP) - pro-inflammatory cytokine and antimicrobial peptide.
Biochimica et biophysica acta. Molecular cell research, 120127
Citation
Döhner, Katinka; John, Ojonugwa Precious; Werfel, Thomas. (2026). Thymic stromal lymphopoietin (TSLP) - pro-inflammatory cytokine and antimicrobial peptide.. Biochimica et biophysica acta. Molecular cell research, 120127. https://doi.org/10.1016/j.bbamcr.2026.120127