Signaling through CD40 ligand decreases CD80 expression on murine Langerhans cells and enhances IL-12 p40 production.
We previously showed that murine Langerhans cells (LC) express CD40 ligand (CD40L). In this study, we further investigated the function of CD40L on LC using agonistic antibodies and CD40L knockout (KO) mice. Signaling through CD40L decreased CD80 expression on LC 48 h after stimulation and the decrease was more remarkable in the presence of interferon-gamma (IFN-gamma). Signaling through CD40 enhanced the production of IL-12 p40 from LC, and simultaneous signaling through CD40L slightly augmented this effect. Addition of IFN-gamma further enhanced IL-12 p40 production. LC from CD40L KO mice expressed similar levels of surface molecules such as CD40, CD80, CD86, and MHC class II, compared with those from wild-type mice. However, they produced less amount of IL-12 p40 during 48 h after purification. These results suggest that signaling through CD40L on LC is important in regulating IL-12 production, which is critical for Th1 type immune responses.
Sugaya
Makoto
M
Department of Dermatology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Nakamura
Koichiro
K
Asahina
Akihiko
A
Fujita
Hideki
H
Tada
Yayoi
Y
Torii
Hideshi
H
Tamaki
Kunihiko
K
D000818:Animals; D015153:Blotting, Western; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000096:biosynthesis*; D007801:Langerhans Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction
D023201:CD40 Ligand; D018664:Interleukin-12