title: Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4⁺ T cells.
abstract: The autoimmune regulator (Aire) is essential for prevention of autoimmunity; its role is best understood in the thymus, where it promotes self-tolerance through tissue-specific antigen (TSA) expression. Recently, extrathymic Aire-expressing cells (eTACs) have been described in murine secondary lymphoid organs, but the identity of such cells and their role in immune tolerance remains unclear. Here we have shown that eTACs are a discrete major histocompatibility complex class II (MHC II)(hi), CD80(lo), CD86(lo), epithelial cell adhesion molecule (EpCAM)(hi), CD45(lo) bone marrow-derived peripheral antigen-presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4⁺ T cells through a mechanism that does not require regulatory T cells (Treg) and is resistant to innate inflammatory stimuli. Together, these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143-0540, USA; Department of Surgery, University of California, San Francisco, San Francisco, CA 94143-0540, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Gardner
authors.forename: Todd C
authors.initials: TC
authors.lastname: Metzger
authors.forename: Eileen J
authors.initials: EJ
authors.lastname: McMahon
authors.forename: Byron B
authors.initials: BB
authors.lastname: Au-Yeung
authors.forename: Anna K
authors.initials: AK
authors.lastname: Krawisz
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Price
authors.forename: Kellsey P
authors.initials: KP
authors.lastname: Johannes
authors.forename: Ansuman T
authors.initials: AT
authors.lastname: Satpathy
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Kristin V
authors.initials: KV
authors.lastname: Tarbell
authors.forename: Arthur
authors.initials: A
authors.lastname: Weiss
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D015551:Autoimmunity; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D017634:Self Tolerance; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D000949:Histocompatibility Antigens Class II; D017493:Leukocyte Common Antigens; D014157:Transcription Factors; D000096927:AIRE Protein