LL-37-Reactive T Cells in Lupus Drive Autoantibody Production Through a Unique Immune Mechanism
45% of SLE patients had LL-37-reactive T follicular helper cells that correlated with disease activity and autoantibody levels, distinct from the Th17 response in psoriasis.
Quick Facts
What This Study Found
45% of SLE patients had circulating T cells that responded strongly to LL37. These T cell levels correlated with anti-LL37 antibody levels and disease activity.
Unlike psoriasis, where LL37-specific T cells are Th17 cells, the SLE LL37-specific T cells displayed a T-follicular helper (TFH)-like phenotype with CXCR5, Bcl-6, and IL-21 expression. This profile is designed to help B cells produce antibodies.
Citrullinated LL37 (cit-LL37) was found abundantly in SLE tissues (skin and kidney). SLE T cells showed much stronger reactivity to cit-LL37 compared to native LL37. In functional assays, these T cells promoted B cell secretion of pathogenic anti-LL37 antibodies.
Key Numbers
45% had LL37-reactive T cells; TFH phenotype (CXCR5+/Bcl-6+/IL-21+); stronger cit-LL37 reactivity; correlated with antibodies and disease activity
How They Did This
Researchers analyzed blood samples from SLE patients for LL37-reactive T cells using flow cytometry and functional assays. They characterized T cell phenotype (TFH markers), tested reactivity to native vs citrullinated LL37, and performed B cell co-culture assays to measure antibody production. Tissue samples were analyzed for cit-LL37 presence.
Why This Research Matters
This study reveals that the same autoantigen (LL37) drives different immune responses depending on the disease. In psoriasis, it triggers inflammation through Th17 cells. In lupus, it drives autoantibody production through follicular helper T cells. Understanding this distinction could lead to disease-specific treatments.
The strong reactivity to citrullinated LL37 suggests that post-translational modifications of self-proteins are important triggers for lupus autoimmunity.
The Bigger Picture
LL-37 is the same autoantigen in both psoriasis and lupus, but drives completely different immune responses. Understanding these disease-specific mechanisms could lead to targeted therapies that address the specific immune pathology in each disease rather than broadly suppressing immunity.
What This Study Doesn't Tell Us
The study shows association between LL37-reactive T cells and disease activity but cannot prove causation. It is unclear whether these T cells drive disease or are a consequence of it.
The sample sizes for SLE patient subgroup analyses were not detailed in the abstract.
Questions This Raises
- ?Could blocking LL-37-reactive TFH cells reduce lupus autoantibody production?
- ?Does citrullination of LL-37 happen more in lupus than healthy individuals?
- ?Are LL-37-reactive T cell levels useful as a lupus biomarker?
Trust & Context
- Key Stat:
- 45% of SLE patients have LL-37-reactive TFH cells that correlate with disease activity — a distinct autoimmune mechanism from psoriasis
- Evidence Grade:
- Moderate evidence from human observational immunology study. Association established but causation not proven.
- Study Age:
- Published in 2020. LL-37 autoimmunity research continues across multiple diseases.
- Original Title:
- Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.
- Published In:
- Scientific reports, 10(1), 5851 (2020)
- Authors:
- Lande, R, Palazzo, R, Gestermann, N, Jandus, C, Falchi, M, Spadaro, F, Riccieri, V, James, E A, Butera, A, Boirivant, M, Feldmeyer, L, Surbeck, I, Di Lucca, J, Stuber, F, Spinelli, F R, Botti, E, Marinari, B, Bianchi, L, Pica, R, Cerbelli, B, Giannakakis, K, Auteri, S E, Daniels, I, Durrant, L G, Horstman, S, Costanzo, A, Romero, P, Alessandri, C, Conti, F, Valesini, G, Gilliet, M, Chizzolini, C, Frasca, L
- Database ID:
- RPEP-04920
Evidence Hierarchy
Frequently Asked Questions
What does LL-37 have to do with lupus?
LL-37 is a natural antimicrobial peptide. In lupus, the immune system mistakenly treats LL-37 as a foreign invader, producing T cells and antibodies against it. This autoimmune response contributes to disease.
Why does the same protein cause different diseases (psoriasis vs lupus)?
The type of immune response matters. In psoriasis, LL-37 triggers Th17 inflammation (skin disease). In lupus, it triggers TFH cells (autoantibody production, systemic disease). Same trigger, different immune wiring, different disease.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-04920APA
Lande, R; Palazzo, R; Gestermann, N; Jandus, C; Falchi, M; Spadaro, F; Riccieri, V; James, E A; Butera, A; Boirivant, M; Feldmeyer, L; Surbeck, I; Di Lucca, J; Stuber, F; Spinelli, F R; Botti, E; Marinari, B; Bianchi, L; Pica, R; Cerbelli, B; Giannakakis, K; Auteri, S E; Daniels, I; Durrant, L G; Horstman, S; Costanzo, A; Romero, P; Alessandri, C; Conti, F; Valesini, G; Gilliet, M; Chizzolini, C; Frasca, L. (2020). Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.. Scientific reports, 10(1), 5851. https://doi.org/10.1038/s41598-020-62480-3
MLA
Lande, R, et al. "Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.." Scientific reports, 2020. https://doi.org/10.1038/s41598-020-62480-3
RethinkPeptides
RethinkPeptides Research Database. "Native/citrullinated LL37-specific T-cells help autoantibody..." RPEP-04920. Retrieved from https://rethinkpeptides.com/research/lande-2020-nativecitrullinated-ll37specific-tcells-help
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.