TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25695838.
- Also identified by DOI 10.1038/ncomms7329 and PMC identifier 4346620.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Autoantibodies induce various autoimmune diseases, including systemic lupus erythematosus (SLE). We previously described that CD4(+)CD25(-)LAG3(+) regulatory T cells (LAG3(+) Treg) are regulated by Egr2, a zinc-finger transcription factor required for the induction of T-cell anergy. We herein demonstrate that LAG3(+) Treg produce high amounts of TGF-β3 in an Egr2- and Fas-dependent manner. LAG3(+) Treg require TGF-β3 to suppress B-cell responses in a murine model of lupus. Moreover, TGF-β3- and LAG3(+) Treg-mediated suppression requires PD-1 expression on B cells. We also show that TGF-β3-expressing human LAG3(+) Treg suppress antibody production and that SLE patients exhibit decreased frequencies of LAG3(+) Treg. These results clarify the mechanism of B-cell regulation and suggest therapeutic strategies.
Medical subject headings
- CD4-Positive T-Lymphocytes
- Early Growth Response Protein 2
- Immunity, Humoral
- Lupus Erythematosus, Systemic
- Transforming Growth Factor beta3