TGF-β3-expressing CD4+CD25(-)LAG3+ regulatory T cells control humoral immune responses.

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.

• Authors: Tomohisa Okamura, Shuji Sumitomo, Kaoru Morita, Yukiko Iwasaki, Mariko Inoue, Shinichiro Nakachi, Toshihiko Komai, Hirofumi Shoda, Jun-Ichi Miyazaki, Keishi Fujio, Kazuhiko Yamamoto
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 6329 (Feb 19 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 25695838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• EGR2 protein, human
• Early Growth Response Protein 2
• Egr2 protein, mouse
• IL2RA protein, human
• Interleukin-2 Receptor alpha Subunit
• TGFB3 protein, human
• Tgfb3 protein, mouse
• Transforming Growth Factor beta3
• Lymphocyte Activation Gene 3 Protein

Topics

• Animals
• Antigens, CD (metabolism)
• B-Lymphocytes (cytology)
• CD4-Positive T-Lymphocytes (cytology)
• Disease Models, Animal
• Early Growth Response Protein 2 (metabolism)
• Female
• Humans
• Immunity, Humoral (immunology)
• Interleukin-2 Receptor alpha Subunit (metabolism)
• Lupus Erythematosus, Systemic (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Spleen (metabolism)
• T-Lymphocytes, Regulatory (cytology)
• Transforming Growth Factor beta3 (metabolism)
• Lymphocyte Activation Gene 3 Protein