title: Dexamethasone promotes tolerance in vivo by enriching CD11clo CD40lo tolerogenic macrophages.
abstract: We previously showed that antigen immunization in the presence of the immunosuppressant dexamethasone (a strategy we termed "suppressed immunization") could tolerize established recall responses of T cells. However, the mechanism by which dexamethasone acts as a tolerogenic adjuvant has remained unclear. In the present study, we show that dexamethasone enriches CD11c(lo) CD40(lo)  macrophages in a dose-dependent manner in the spleen and peripheral lymph nodes of mice by depleting all other CD11c(+) CD40(+)  cells including dendritic cells. The enriched macrophages display a distinct MHC class II (MHC II)(lo) CD86(hi)  phenotype. Upon activation by antigen in vivo, CD11c(lo) CD40(lo)  macrophages upregulate IL-10, a classic marker for tolerogenic antigen-presenting cells, and elicit a serum IL-10 response. When presenting antigen in vivo, these cells do not elicit recall responses from memory T cells, but rather stimulate the expansion of antigen-specific regulatory T cells. Moreover, the depletion of CD11c(lo) CD40(lo)  macrophages during suppressed immunization diminishes the tolerogenic efficacy of the treatment. These results indicate that dexamethasone acts as a tolerogenic adjuvant partly by enriching the CD11c(lo) CD40(lo)  tolerogenic macrophages.
authors.affiliation: Department of Biomedical Sciences, University of Illinois at Chicago, Chicago, Illinois 61107, USA. guoxingz@uic.edu
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zheng
authors.forename: Shibo
authors.initials: S
authors.lastname: Zhong
authors.forename: Yajun
authors.initials: Y
authors.lastname: Geng
authors.forename: Gnanasekar
authors.initials: G
authors.lastname: Munirathinam
authors.forename: Isaac
authors.initials: I
authors.lastname: Cha
authors.forename: Catherine
authors.initials: C
authors.lastname: Reardon
authors.forename: Godfrey S
authors.initials: GS
authors.lastname: Getz
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Youmin
authors.initials: Y
authors.lastname: Kang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Aoshuang
authors.initials: A
authors.lastname: Chen
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D018845:CD11 Antigens / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000188:drug therapy* / Q000276:immunology; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016753:Interleukin-10 / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D018845:CD11 Antigens; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D003907:Dexamethasone