Reverse signaling using an inducible costimulator to enhance immunogenic function of dendritic cells.
A costimulatory signal from an inducible costimulator (ICOS) of T cells plays a critical role in immunological homeostasis. This study shows that the interaction of ICOSIg and its ligand (ICOSL) on mouse bone marrow-derived dendritic cells (DCs) induces a p38-MAPK dependent elevation of interleukin 6 (IL-6). It also enhances phagocytosis and the antigen-presentation function of DCs in vitro, further favoring cell-mediated immunity in vivo. As seen for other types of costimulator molecules expressed in the T cells in the CD28 family, it is shown here for the first time that ICOS can also deliver reverse signals through its ligand to ICOSL-expressing cells. These reverse signals in turn transfer positive immunogenic information to bone marrow-derived DCs. Our work therefore provides new recognition of an ICOSL/ICOS signal pathway in immunity and also supplies more evidence that this ICOSL/ICOS signal pathway is a reasonable target for therapeutic drugs.
Tang
Gusheng
G
Department of Laboratory Diagnosis, Changhai Hospital, The Second Military Medical University, Room 701, Building of Laboratory Medicine and Technology, Number 168, Shanghai, China.
Qin
Qin
Q
Zhang
Peng
P
Wang
Guifang
G
Liu
Menglei
M
Ding
Qingli
Q
Qin
Yanghua
Y
Shen
Qian
Q
D000818:Animals; D017951:Antigen Presentation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001854:Bone Marrow Cells; D003713:Dendritic Cells / Q000276:immunology*; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D015850:Interleukin-6; D011506:Proteins; D048051:p38 Mitogen-Activated Protein Kinases