title: Dendritic-cell-associated C-type lectin 2 (DCAL-2) alters dendritic-cell maturation and cytokine production.
abstract: Dendritic-cell (DC)-associated C-type lectin receptors (CLRs) take up antigens to present to T cells and regulate DC functions. DCAL-2 is a CLR with a cytosolic immunoreceptor tyrosine-based inhibitory motif (ITIM), which is restricted to immature DCs (iDCs), monocytes, and CD1a+ DCs. Cross-linking DCAL-2 on iDCs induced protein tyrosine phosphorylation and MAPK activation as well as receptor internalization. To test if DCAL-2 is involved in DC maturation and cytokine expression, we stimulated iDCs with anti-DCAL-2 mAb with or without LPS, zymosan, or CD40L. While anti-DCAL-2 did not induce iDCs to mature, it did up-regulate CCR7 expression and IL-6 and IL-10 production. DCAL-2 signals augmented DC maturation induced by LPS or zymosan, increasing both CCR7 and DC-LAMP expression. Of interest, DCAL-2 ligation had the opposite effects on TLR versus CD40L signaling: anti-DCAL-2 suppressed TLR-induced IL-12 expression, but significantly enhanced CD40L-induced IL-12 production. DCAL-2 ligation also suppressed the ability of TLR-matured DCs to induce IFN-gamma-secreting Th1 cells but augmented the capacity of CD40L-matured DCs to polarize naive T cells into Th1 cells. Thus, DCAL-2 may program DCs differently depending on whether DCs are signaled via TLRs or by T cells. DCAL-2 may be a potential immunotherapeutic target for modulating autoimmune diseases or for developing vaccines.
authors.affiliation: Department of Immunology, Box 357330, University of Washington, Seattle, WA 98195, USA. chenc2@u.washington.edu
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Helen
authors.initials: H
authors.lastname: Floyd
authors.forename: N Eric
authors.initials: NE
authors.lastname: Olson
authors.forename: Dario
authors.initials: D
authors.lastname: Magaletti
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.forename: Kevin
authors.initials: K
authors.lastname: Draves
authors.forename: Edward A
authors.initials: EA
authors.lastname: Clark
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000097:blood; D001483:Base Sequence; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D010802:Phylogeny; D011975:Receptors, Mitogen / Q000235:genetics* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C485220:CLEC12A protein, human; D016207:Cytokines; D037181:Lectins, C-Type; D011975:Receptors, Mitogen