title: Novel immunomodulatory effects of adiponectin on dendritic cell functions.
abstract: Adiponectin (ADN) is an adipocytokine with anti-inflammatory properties. Although it has been reported that ADN can inhibit the immunostimulatory function of monocytes and macrophages, little is known of its effect on dendritic cells (DC). Recent data suggest that ADN can regulate immune responses. DCs are uniquely specialised antigen presenting cells that play a central role in the initiation of immunity and tolerance. In this study, we have investigated the immuno- modulatory effects of ADN on DC functions. We found that ADN has only moderate effect on the differentiation of murine bone marrow (BM) derived DCs but altered the phenotype of DCs. The expression of major histocompatibilty complex class II (MHCII), CD80 and CD86 on ADN conditioned DCs (ADN-DCs) was lower than that on untreated cells. The production of IL-12p40 was also suppressed in ADN-DCs. Interestingly, ADN treated DCs showed an increase in the expression of the inhibitory molecule, programmed death-1 ligand (PDL-1) compared to untreated cells. In vitro co-culture of ADN-DCs with allogeneic T cells led to a decrease in T cell proliferation and reduction of IL-2 production. Concomitant with that, a higher percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) was detected in co-cultures of T cells and ADN-DCs. Blocking PD-1/PDL-1 pathway could partially restore T cell function. These findings suggest that the immunomodulatory effect of ADN on immune responses could be at least partially be mediated by its ability to alter DC function. The PD-1/PDL-1 pathway and the enhancement of Treg expansion are implicated in the immunomodulatory mechanisms.
authors.affiliation: Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China; Research Centre of Infection and Immunity, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Julia Yuen Shan
authors.initials: JY
authors.lastname: Tsang
authors.forename: Daxu
authors.initials: D
authors.lastname: Li
authors.forename: Derek
authors.initials: D
authors.lastname: Ho
authors.forename: Jiao
authors.initials: J
authors.lastname: Peng
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lamb
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Paul Kwong Hang
authors.initials: PK
authors.lastname: Tam
mesh_terms: D052242:Adiponectin / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D056747:Immunomodulation; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D052242:Adiponectin; D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053762:Interleukin-12 Subunit p40