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.
45% of SLE patientshave LL-37-reactive TFH cells that correlate with disease activity — a distinct autoimmune mechanism from psoriasis
What the researchers 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.
Why it 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 numbers in context
45% had LL37-reactive T cells; TFH phenotype (CXCR5+/Bcl-6+/IL-21+); stronger cit-LL37 reactivity; correlated with antibodies and disease activity
How the study worked
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.
Who was studied
Systemic lupus erythematosus patients (human)
What this study cannot 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.
How to read the evidence
Moderate evidence from human observational immunology study. Association established but causation not proven.
When this study was published
Published in 2020. LL-37 autoimmunity research continues across multiple diseases.
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.
Questions still open
- 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?
Common questions
What does LL-37 have to do with lupus?
Why does the same protein cause different diseases (psoriasis vs lupus)?
Read the original research
Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.
Scientific reports, 10(1), 5851
Citation
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