NF-κB: At the Borders of Autoimmunity and Inflammation

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory response. In the first part of this review, we discuss the NF-κB inducers, signaling pathways, and regulators involved in immune homeostasis as well as d...

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Veröffentlicht in:	Frontiers in immunology Jg. 12; S. 716469
Hauptverfasser:	Barnabei, Laura, Laplantine, Emmanuel, Mbongo, William, Rieux-Laucat, Frédéric, Weil, Robert
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Switzerland Frontiers 09.08.2021 Frontiers Media S.A
Schlagworte:	Animals Autoimmune Diseases - etiology Autoimmune Diseases - metabolism autoimmunity Autoimmunity - genetics autoinflammation Carrier Proteins - metabolism Disease Management Disease Susceptibility genetic diseases Genetic Predisposition to Disease Humans Immune Checkpoint Proteins - genetics Immune Tolerance Immunology Inflammation - etiology Inflammation - metabolism Inflammation - pathology Inflammation - therapy Life Sciences Molecular Targeted Therapy NF-kappa B - genetics NF-kappa B - metabolism NF-κB Protein Binding Signal Transduction T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Ubiquitin-Protein Ligases - metabolism ubiquitination genetic diseases autoinflammation NF-κB immune tolerance autoimmunity ubiquitination NF-kB
ISSN:	1664-3224, 1664-3224
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Zusammenfassung:	The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory response. In the first part of this review, we discuss the NF-κB inducers, signaling pathways, and regulators involved in immune homeostasis as well as detail the importance of post-translational regulation by ubiquitination in NF-κB function. We also indicate the stages of central and peripheral tolerance where NF-κB plays a fundamental role. With respect to central tolerance, we detail how NF-κB regulates medullary thymic epithelial cell (mTEC) development, homeostasis, and function. Moreover, we elaborate on its role in the migration of double-positive (DP) thymocytes from the thymic cortex to the medulla. With respect to peripheral tolerance, we outline how NF-κB contributes to the inactivation and destruction of autoreactive T and B lymphocytes as well as the differentiation of CD4 + -T cell subsets that are implicated in immune tolerance. In the latter half of the review, we describe the contribution of NF-κB to the pathogenesis of autoimmunity and autoinflammation. The recent discovery of mutations involving components of the pathway has both deepened our understanding of autoimmune disease and informed new therapeutic approaches to treat these illnesses.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology Edited by: Howard A Young, National Cancer Institute at Frederick, United States Reviewed by: Ruaidhri Carmody, University of Glasgow, United Kingdom; Patrick Leung, University of California, Davis, United States
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2021.716469