title: Molecular underpinnings of Th17 immune-regulation and their implications in autoimmune diabetes.
abstract: The emergence of Th17 cells as a unique sub-population of CD4(+) T cells has revolutionized the current understanding of adaptive immune system and autoimmune diseases. Th17 cells are characterized by the expression of effector cytokines IL-17A, IL-17F, IL-21 and IL-22, and lineage specific transcription factor ROR-C in human and ROR-γt in mice. Generation and differentiation of Th17 cells from naive CD4(+) T cells is driven by transforming growth factor (TGF)-β, IL-6, IL-23, IL-1β and IL-21. Recent studies suggest that the pathogenicity of Th17 cells is determined by the presence of IL-23 and TGF-β3 in local micro-environment. Emerging reports highlight the importance of T-helper cell plasticity in pathogenesis of various autoimmune diseases. Th17 cells exhibit significant plasticity and converted to Th1-like cells under pathogenic conditions. Albeit growing body of evidences stating a pathogenic role for Th17 cells in autoimmune diabetes, conflicting reports also state an indifferent or protective role for Th17 cells. The operating mechanisms modulating Th17 immune response in autoimmune diabetes remain elusive. This review discusses recent advances in the understanding of transcriptional and post-transcriptional mechanisms of Th17 polarization, factors influencing pathogenicity of Th17 cells, molecular mechanisms of Th17/Th1 and Treg/Th17 plasticity and implications of these phenomena in autoimmune diabetes.
authors.affiliation: Department of Biomedical Science, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India. Electronic address: praba.biopioneer@gmail.com.
authors.forename: Prabhakaran
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Madurai Government Medical College, Madurai, Tamil Nadu, India.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Subramaniyam
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002454:Cell Differentiation; D019070:Cell Lineage; D019175:DNA Methylation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D018417:Th1 Cells / Q000166:cytology; D058504:Th17 Cells / Q000166:cytology*; D014158:Transcription, Genetic
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D035683:MicroRNAs
keywords: Autoimmune diabetes; IL-17; ROR-γt; T-helper cell plasticity; Th17 cells