Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8537025 | Pharmacology & Therapeutics | 2017 | 26 Pages |
Abstract
AA is a presumptive autoimmune disorder that coincides and genetically clusters to several other autoimmune diseases. In this review, we pay attention to the learnings from the mechanistic research and drug development in these other autoimmune conditions. Interestingly, most of these diseases have been linked to compromised central and peripheral tolerance, and increased intestinal inflammation with enhanced gut permeability. Break of tolerance and priming of the autoreactive T-cells to attack antigenic epitopes in the hair follicle most likely requires several steps which include escape from negative selection and compromised peripheral tolerance. Local skin-related changes are also of importance due to the patchy manifestation of the skin areas with loss of hair, particularly in the early disease. Here, we discuss the defective mechanisms of tolerance, both central and peripheral, and hypothesize that the disease is driven by areas of tolerance break, and that these could be targeted for successful therapeutic interventions.
Keywords
TGFAutoimmune polyendocrine syndromemTECnatural killer group 2Dalopecia areataCTLANKG2DTregsCXCLT1DTregILCEAEAPCSCFATECFOXP3CEDnatural killerAPsRheumatoid arthritisHuman leukocyte antigenantigen-presenting cellsHLAexperimental autoimmune encephalomyelitisshort-chain fatty acidImmune privilegeIFNinterleukinAutoimmune diseaseCeliac diseasetransforming growth factorToleranceautoimmune regulatorautoimmunityexcretory/secretoryType 1 diabetesDysbiosisRegulatory T celltolerogenic dendritic cellDendritic cellinnate lymphoid cellthymic epithelial cellmedullary thymic epithelial cellHelminth infectionHair follicleSystemic lupus erythematosusSLEchemokine (C-X-C motif) ligand major histocompatibility complexMHCMultiple sclerosistraAIREAID
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Pharmacology
Authors
Gabriel Skogberg, Sonya Jackson, Annika Ã
strand,