title: Adipocytes as immune regulatory cells.
abstract: Obesity is a chronic inflammatory state and adipocytes are capable of contributing to this inflammation by their production of inflammatory mediators. The present study used fibroblast-derived adipocytes and normal spleen cells as a model to determine if adipocytes can also serve as immune regulatory cells by modulating the functions of conventional immune cells. Media conditioned by the adipocytes stimulated release of the Th1-type cytokines IL-2, IFN-γ and GM-CSF from cultures of normal spleen cells. The adipocytes also stimulated spleen cell release of inhibitory cytokines, although to varying degrees. This included IL-10, IL-13 and, to a lesser extent, IL-4. Spleen cell production of the inflammatory cytokines IL-6, TNF-α and IL-9 was stimulated by adipocytes, although production of the Th17-derived cytokine, IL-17, was not stimulated. The adipocyte-conditioned medium did not stimulate production of predominantly monocytes-derived chemokines CXCL9, CCL2, CCL3, CCL4, but stimulated production of the predominantly T-cell-derived chemokine CCL5. In all cases where cytokine/chemokine production from spleen cells was stimulated by adipocytes, it was to a far greater level than was produced by the adipocytes themselves. Studies initiated to determine the identity of the adipocyte-derived mediators showed that the spleen cell modulation could not be attributed to solely adiponectin or leptin. Studies to determine the source of some of the cytokines whose production was stimulated by adipocytes showed that expression of the inflammatory cytokine IL-6 was not increased in either CD4(+) or CD8(+) T-cell. When the splenic T-cells were examined for IFN-γ, the adipocyte stimulation of IFN-γ was within CD8(+) T-cells, not CD4(+) T-cells. These studies show that adipocytes may be able to serve as immune regulatory cells to stimulate conventional immune cells to release a spectrum of immune mediators.
authors.affiliation: Department of Otolaryngology, Medical University of South Carolina, Charleston, SC 29425, United States. vielmasa@musc.edu
authors.forename: Silvana A
authors.initials: SA
authors.lastname: Vielma
authors.forename: Richard L
authors.initials: RL
authors.lastname: Klein
authors.forename: Corinne A
authors.initials: CA
authors.lastname: Levingston
authors.forename: M Rita I
authors.initials: MR
authors.lastname: Young
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000276:immunology*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines