Identification of a novel marker for dendritic cell maturation, mouse transmembrane protein 123.
Dendritic cells (DCs) are a group of professional antigen-presenting cells, and many genes are known to be associated with their maturation. We compared the transcriptional profiles of immature and mature mouse Langerhans cells using the suppressive, subtractive hybridization method and identified a novel gene of unknown function, termed herein transmembrane protein 123 (Tmem123), of which mRNA expression was enhanced in mature but not in immature Langerhans cells. Its expression was also enhanced in other mature DCs such as bone marrow-derived DCs (BMDCs) and splenic DCs. Interestingly, CD40 expression was up-regulated on mature BMDCs cultured with colchicine concurrently with the enhanced expression of Tmem123 compared with that of fresh BMDCs. Furthermore, the expression of CD40 was enhanced on Tmem123-transfected DC2.4 cells, a mouse BMDC-derived cell line, compared with that on mock-transfected DC2.4 cells. This enhancement of CD40 expression did not occur after deletion of lysosome/endosome targeting YXXϕ motifs (where X is any amino acid and ϕ is a bulky hydrophobic amino acid) in the Tmem123 cytoplasmic tail. By stimulation with anti-CD40 monoclonal antibody, these transfectants secreted an increased amount of IL-12/23 p40 compared with mock-transfected DC2.4 cells. Thus, our study demonstrates that Tmem123 may be used as a new maturation marker in DCs and that this molecule may be closely associated with the cell surface expression of CD40.
Takekoshi
Tomonori
T
Department of Dermatology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Tada
Yayoi
Y
Watanabe
Takahiro
T
Sugaya
Makoto
M
Hoashi
Toshihiko
T
Komine
Mayumi
M
Kawashima
Tomohiko
T
Shimizu
Teruo
T
Hau
Carren Sy
CS
Asahina
Akihiko
A
Yokomizo
Takehiko
T
Sato
Shinichi
S
Tamaki
Kunihiko
K
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007801:Langerhans Cells / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis*; D011956:Receptors, Cell Surface; D017384:Sequence Deletion; D013154:Spleen / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
D019013:CD40 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C553234:Tmem123 protein, mouse