title: C-type lectin MCL is an FcRγ-coupled receptor that mediates the adjuvanticity of mycobacterial cord factor.
abstract: Cord factor, also called trehalose-6,6'-dimycolate (TDM), is a potent mycobacterial adjuvant. We herein report that the C-type lectin MCL (also called Clec4d) is a TDM receptor that is likely to arise from gene duplication of Mincle (also called Clec4e). Mincle is known to be an inducible receptor recognizing TDM, whereas MCL was constitutively expressed in myeloid cells. To examine the contribution of MCL in response to TDM adjuvant, we generated MCL-deficient mice. TDM promoted innate immune responses, such as granuloma formation, which was severely impaired in MCL-deficient mice. TDM-induced acquired immune responses, such as experimental autoimmune encephalomyelitis (EAE), was almost completely dependent on MCL, but not Mincle. Furthermore, by generating Clec4e(gfp) reporter mice, we found that MCL was also crucial for driving Mincle induction upon TDM stimulation. These results suggest that MCL is an FcRγ-coupled activating receptor that mediates the adjuvanticity of TDM.
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Miyake
authors.forename: Kenji
authors.initials: K
authors.lastname: Toyonaga
authors.forename: Daiki
authors.initials: D
authors.lastname: Mori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Akiko
authors.initials: A
authors.lastname: Oyamada
authors.forename: Hisakata
authors.initials: H
authors.lastname: Yamada
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Ono
authors.forename: Mikita
authors.initials: M
authors.lastname: Suyama
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D003311:Cord Factors / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000382:microbiology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009164:Mycobacterium Infections / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C113583:Clecsf8 protein, mouse; D003311:Cord Factors; D037181:Lectins, C-Type; D008565:Membrane Proteins; D017452:Receptors, IgG