TY - JOUR
T1 - Role of the NF-kB family member RelB in regulation of Foxp3 + regulatory t cells in vivo
AU - Li, Junhui
AU - Chen, Shuqiu
AU - Chen, Wenhao
AU - Ye, Qifa
AU - Dou, Yaling
AU - Xiao, Yue
AU - Zhang, Lei
AU - Minze, Laurie J.
AU - Li, Xian C.
AU - Xiao, Xiang
N1 - Funding Information:
*Immunobiology and Transplant Science Center, Houston Methodist Hospital, Texas Medical Center, Houston, TX 77030; †Center for Organ Transplant, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Third Xiangya Hospital, Central South University, Changsha, Hunan 410003, China; and ‡Department of Urology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, China
Funding Information:
Received for publication September 13, 2017. Accepted for publication December 4, 2017. This work was supported by grants from the National Institutes of Health (R01AI106200 and R56AI129906) and the Kleberg Foundation.
Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018/2/15
Y1 - 2018/2/15
N2 - The NF-kB family member RelB is an important transcription factor that is capable of regulating diverse immune and inflammatory responses. However, its role in the regulation of Foxp3 + regulatory T cells (Tregs) in vivo is poorly defined. In this study, we demonstrated that germline deletion of Relb resulted in systemic autoimmunity, which is associated with significant accumulation of Foxp3 + Tregs in lymphoid and nonlymphoid organs. Foxp3 + Tregs from RelB-deficient mice were functional and capable of suppressing T effector cells in vitro and in vivo, but Foxp3 2 T effector cells from RelB-deficient mice showed features of hyperactivation and spontaneously produced high levels of IL-2. Surprisingly, mice with conditional deletion of Relb in T cells (Cd4 Cre Relb f/f mice) or specifically in Foxp3 + Tregs (Foxp3 Cre Relb f/f mice) did not show signs of autoimmunity and had similar frequencies of Foxp3 + Tregs in the periphery as wild-type C57BL/6 controls. Both strains of conditional knockout mice also had a normal conventional T cell compartment. However, reconstituting Rag-1 2 / 2 Relb 2 / 2 hosts with wild-type C57BL/6 bone marrow cells led to hyperactivation of T effector cells, as well as marked expansion of Foxp3 + T cells. These data suggest that the autoimmune phenotype in germline RelB-deficient mice is most likely caused by T cell–extrinsic mechanisms, and further studies are warranted to uncover such mechanisms. The Journal of Immunology, 2018, 200: 1325–1334.
AB - The NF-kB family member RelB is an important transcription factor that is capable of regulating diverse immune and inflammatory responses. However, its role in the regulation of Foxp3 + regulatory T cells (Tregs) in vivo is poorly defined. In this study, we demonstrated that germline deletion of Relb resulted in systemic autoimmunity, which is associated with significant accumulation of Foxp3 + Tregs in lymphoid and nonlymphoid organs. Foxp3 + Tregs from RelB-deficient mice were functional and capable of suppressing T effector cells in vitro and in vivo, but Foxp3 2 T effector cells from RelB-deficient mice showed features of hyperactivation and spontaneously produced high levels of IL-2. Surprisingly, mice with conditional deletion of Relb in T cells (Cd4 Cre Relb f/f mice) or specifically in Foxp3 + Tregs (Foxp3 Cre Relb f/f mice) did not show signs of autoimmunity and had similar frequencies of Foxp3 + Tregs in the periphery as wild-type C57BL/6 controls. Both strains of conditional knockout mice also had a normal conventional T cell compartment. However, reconstituting Rag-1 2 / 2 Relb 2 / 2 hosts with wild-type C57BL/6 bone marrow cells led to hyperactivation of T effector cells, as well as marked expansion of Foxp3 + T cells. These data suggest that the autoimmune phenotype in germline RelB-deficient mice is most likely caused by T cell–extrinsic mechanisms, and further studies are warranted to uncover such mechanisms. The Journal of Immunology, 2018, 200: 1325–1334.
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U2 - 10.4049/jimmunol.1701310
DO - 10.4049/jimmunol.1701310
M3 - Article
C2 - 29298831
AN - SCOPUS:85044755298
SN - 0022-1767
VL - 200
SP - 1325
EP - 1334
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -