TY - JOUR
T1 - Cutting edge
T2 - Origins, recruitment, and regulation of CD11c+ cells in inflamed islets of autoimmune diabetes mice
AU - Klementowicz, Joanna E.
AU - Mahne, Ashley E.
AU - Spence, Allyson
AU - Nguyen, Vinh
AU - Satpathy, Ansuman T.
AU - Murphy, Kenneth M.
AU - Tang, Qizhi
N1 - Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - In NOD mice, CD11c+ cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic b cells. In this study, we investigated their origin and mechanism of recruitment. CD11c+ cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c+ cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c+ cells was partially dependent on their receptor Ccr5. Treatment with islet Agspecific regulatory T cells led to a marked decrease of Ccl5 and Ccl8, and a reduction of monocyte recruitment. These results implicate a monocytic origin of CD11c+ cells in inflamed islets and suggest that therapeutic regulatory T cells directly or indirectly regulate their influx by altering the chemotactic milieu in the islets.
AB - In NOD mice, CD11c+ cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic b cells. In this study, we investigated their origin and mechanism of recruitment. CD11c+ cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c+ cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c+ cells was partially dependent on their receptor Ccr5. Treatment with islet Agspecific regulatory T cells led to a marked decrease of Ccl5 and Ccl8, and a reduction of monocyte recruitment. These results implicate a monocytic origin of CD11c+ cells in inflamed islets and suggest that therapeutic regulatory T cells directly or indirectly regulate their influx by altering the chemotactic milieu in the islets.
UR - http://www.scopus.com/inward/record.url?scp=85021138478&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1601062
DO - 10.4049/jimmunol.1601062
M3 - Article
C2 - 28550204
AN - SCOPUS:85021138478
SN - 0022-1767
VL - 199
SP - 27
EP - 32
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -