title: Serum amyloid A overrides Treg anergy via monocyte-dependent and Treg-intrinsic, SOCS3-associated pathways.
abstract: The acute phase protein serum amyloid A (SAA) has been well characterized as an indicator of inflammation. Nevertheless, its functions in pro versus anti-inflammatory processes remain obscure. Here we provide unexpected evidences that SAA induces the proliferation of the tolerogenic subset of regulatory T cells (T(reg)). Intriguingly, SAA reverses T(reg) anergy via its interaction with monocytes to activate distinct mitogenic pathways in T(reg) but not effector T cells. This selective responsiveness of T(reg) correlates with their diminished expression of SOCS3 and is antagonized by T(reg)-specific induction of this regulator of cytokine signaling. Collectively, these evidences suggest a novel anti-inflammatory role of SAA in the induction of a micro-environment that supports T(reg) expansion at sites of infection or tissue injury, likely to curb (auto)-inflammatory responses.
authors.affiliation: Department of Pediatrics, Immunology Program, Stanford University School of Medicine, 259 Campus Drive, Stanford, CA 94305, USA. kdnguyen@stanford.edu
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Nguyen
authors.forename: Claudia
authors.initials: C
authors.lastname: Macaubas
authors.forename: Kari C
authors.initials: KC
authors.lastname: Nadeau
authors.forename: Phi
authors.initials: P
authors.lastname: Truong
authors.forename: Taejin
authors.initials: T
authors.lastname: Yoon
authors.forename: Tzielan
authors.initials: T
authors.lastname: Lee
authors.forename: Jane L
authors.initials: JL
authors.lastname: Park
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D017635:Clonal Anergy / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000685:Serum Amyloid A Protein / Q000494:pharmacology* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology
chemical_list: D000685:Serum Amyloid A Protein; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins