title: Block of both TGF-β and IL-2 signaling impedes Neurophilin-1+regulatory T cell and follicular regulatory T cell development.
abstract: Understanding the mechanisms that lead to autoimmunity is critical for defining potential therapeutic pathways. In this regard there have been considerable efforts in investigating the interacting roles of TGF-β and IL-2 on the function regulatory T cells. We have taken advantage of dnTGF-βRII Il2ra-/-(abbreviated as Il2ra-/-Tg) mouse model, which allows a direct mechanistic approach to define the relative roles of TGF-β and IL-2 on Treg development. Il2ra-/-Tg mice spontaneously developed multi-organ autoimmune diseases with expansion of pathogenic T cells and enhanced germinal center response at 3-4 weeks of age. Importantly, peripheral Treg cells from Il2ra-/-Tg mice demonstrated an activated Th1-like stable phenotype and normal in vitro suppressive function, while thymus Treg increased but manifested decreased suppressive function. Interestingly, neither thymus nor peripheral Treg cells of Il2ra-/-Tg mice contained Neuropilin-1+or PD-1hiphenotype, resulting in defective follicular regulatory T (Tfr) cell development. Such defective Tfr development led to elevated follicular T helper cells, enhanced germinal center responses and increased plasma cell infiltration. These data demonstrate an important synergetic role of TGF-β and IL-2 in the generation, activation and stability of Treg cells, as well as their subsequent development into Tfr cells.
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Liang
authors: L
authors: Li
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Shu-Han
authors: SH
authors: Yang
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Yuan
authors: Y
authors: Yao
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Yu-Qing
authors: YQ
authors: Xie
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Yan-Qing
authors: YQ
authors: Yang
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Yin-Hu
authors: YH
authors: Wang
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Xue-Ying
authors: XY
authors: Yin
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors: Hong-Di
authors: HD
authors: Ma
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, USA.
authors: MEric
authors: M
authors: Gershwin
authors: Liver Immunology Laboratory, Institute of Immunology and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, Hefei 230027, China.
authors: Zhe-Xiong
authors: ZX
authors: Lian
mesh_terms: D000818:Animals; D018858:Germinal Center / Q000378:metabolism; D020104:Immunophilins / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D007376:Interleukin-2 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D000072281:Lymphadenopathy / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008822:Mice, Transgenic; D010641:Phenotype; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D020104:Immunophilins