TY - JOUR
T1 - Extrathymic aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4+ T cells
AU - Gardner, James M.
AU - Metzger, Todd C.
AU - McMahon, Eileen J.
AU - Au-Yeung, Byron B.
AU - Krawisz, Anna K.
AU - Lu, Wen
AU - Price, Jeffrey D.
AU - Johannes, Kellsey P.
AU - Satpathy, Ansuman T.
AU - Murphy, Kenneth M.
AU - Tarbell, Kristin V.
AU - Weiss, Arthur
AU - Anderson, Mark S.
N1 - Funding Information:
We thank M. Cheng for critical reading of the manuscript; J. Esensten, J. Bluestone, Q. Tang, H. van Santen, P. Peterson, H. Scott, E. Unanue, D. Mathis, and C. Benoist for reagents and mice, and N. Killeen and the UCSF Transgenic Core for help generating transgenic mice. This work was supported by the US National Institutes of Health AI035297 (M.S.A), DK59958 and DK063720 for core support, the Helmsley Charitable Trust (M.S.A, T.C.M), the American Diabetes Association (J.M.G.), the UCSF Medical Scientist Training Program (J.M.G.), the UCSF Department of Surgery (J.M.G.), and the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH (J.D.P. and K.V.T.). This research was performed with the support of the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project sponsored by the Juvenile Diabetes Research Foundation International (JDRF). Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at www.jdrfnpod.org/our-partners.php .
PY - 2013/9/19
Y1 - 2013/9/19
N2 - 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, CD80lo, CD86lo, epithelial cell adhesion molecule (EpCAM)hi, CD45lo bone marrow-derived peripheral antigen-presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4+ Tcells through a mechanism that does not require regulatory Tcells (Treg) and is resistant to innate inflammatory stimuli. Together, these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.
AB - 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, CD80lo, CD86lo, epithelial cell adhesion molecule (EpCAM)hi, CD45lo bone marrow-derived peripheral antigen-presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4+ Tcells through a mechanism that does not require regulatory Tcells (Treg) and is resistant to innate inflammatory stimuli. Together, these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.
UR - http://www.scopus.com/inward/record.url?scp=84884332897&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2013.08.005
DO - 10.1016/j.immuni.2013.08.005
M3 - Article
C2 - 23993652
AN - SCOPUS:84884332897
SN - 1074-7613
VL - 39
SP - 560
EP - 572
JO - Immunity
JF - Immunity
IS - 3
ER -