title: c-Rel is Required for the Induction of pTregs in the Eye but Not in the Gut Mucosa.
abstract: Regulatory T (Treg) cells play an integral role in maintaining immune homeostasis and preventing autoimmune diseases. Forkhead box P3 expression marks the commitment of progenitor cells to the Treg lineage. Although the essential function of the nuclear factor (NF)-κB family transcription factor c-Rel in the regulation of natural Treg cells has been firmly established, little is known about whether c-Rel is involved in the in vivo generation of peripheral Treg cells (pTregs), which develop from mature CD4+ conventional T cells outside of the thymus. We sought to answer this question through the induction of pTregs in the eye and gut mucosa using ovalbumin-specific T cell receptor transgenic mice that do or do not express c-Rel. Our results showed that Tregs can be induced in the eye in a c-Rel-dependent manner when immune-mediated inflammation occurs. However, c-Rel is dispensable for the induction of pTregs in the gut mucosa after oral antigen administration. Thus, c-Rel may play distinct roles in regulating the development of pTregs in different organs. Abbreviations ACAID: Anterior Chamber-Associated Immune Deviation; ATF: activating transcription factor; CREB: cAMP responsive element-binding protein; DMEM: Dulbecco minimum essential medium; HBSS: Hanks Balanced Salt Solution; NFAT: Nuclear Factor of Activated T cells; PBS: Phosphate-buffered saline; PE: Phycoerythrin; WT: wild type.
authors.affiliation: a Shandong Eye Institute , Qingdao , People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: a Shandong Eye Institute , Qingdao , People's Republic of China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Shi
authors.affiliation: b Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen , People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Fan
authors.affiliation: b Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen , People's Republic of China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wan
authors.affiliation: c Department of Pathology and Laboratory of Medicine , University of Pennsylvania School of Medicine , Philadelphia , PA , USA.
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
authors.affiliation: b Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen , People's Republic of China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Ruan
mesh_terms: D051697:Activating Transcription Factor 1; D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000276:immunology; D005123:Eye / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology; D009928:Organ Specificity; D010047:Ovalbumin / Q000008:administration & dosage; D020569:Proto-Oncogene Proteins c-rel / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation
chemical_list: D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050778:NFATC Transcription Factors; D020569:Proto-Oncogene Proteins c-rel; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin
keywords: Foxp3; c-Rel; eye; gut mucosa; pTreg