title: A key role for NF-κB transcription factor c-Rel in T-lymphocyte-differentiation and effector functions.
abstract: The transcription factors of the Rel/NF-κB family function as key regulators of innate and adoptive immunity. Tightly and temporally controlled activation of NF-κB-signalling pathways ensures prevention of harmful immune cell dysregulation, whereas a loss of control leads to pathological conditions such as severe inflammation, autoimmune disease, and inflammation-associated oncogenesis. Five family members have been identified in mammals: RelA (p65), c-Rel, RelB, and the precursor proteins NF-κB1 (p105) and NF-κB2 (p100), that are processed into p50 and p52, respectively. While RelA-containing dimers are present in most cell types, c-Rel complexes are predominately found in cells of hematopoietic origin. In T-cell lymphocytes, certain genes essential for immune function such as Il2 and Foxp3 are directly regulated by c-Rel. Additionally, c-Rel-dependent IL-12 and IL-23 transcription by macrophages and dendritic cells is crucial for T-cell differentiation and effector functions. Accordingly, c-Rel expression in T cells and antigen-presenting cells (APCs) controls a delicate balance between tolerance and immunity. This review gives a selective overview on recent progress in understanding of diverse roles of c-Rel in regulating adaptive immunity.
authors.affiliation: Institute for Medical Microbiology and Hygiene, Philipps University of Marburg, Hans Meerwein Strasse 2, 35032 Marburg, Germany. alexander.visekruna@staff.uni-marburg.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Visekruna
authors.forename: Anton
authors.initials: A
authors.lastname: Volkov
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steinhoff
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008322:Mammals; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D055503:Protein Multimerization; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel