%0 Journal Article
%T Th17 Cells in Immunity and Autoimmunity
%A Simone Kennedy Bedoya
%A Brandon Lam
%A Kenneth Lau
%A Joseph Larkin III
%J Journal of Immunology Research
%D 2013
%R 10.1155/2013/986789
%X Th17 and IL-17 play important roles in the clearance of extracellular bacterial and fungal infections. However, strong evidence also implicates the Th17 lineage in several autoimmune disorders including multiple sclerosis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. The Th17 subset has also been connected with type I diabetes, although whether it plays a role in the pathogenicity of or protection from the disease remains a controversial issue. In this review we have provided a comprehensive overview of Th17 pathogenicity and function, including novel evidence for a protective role of Th17 cells in conjunction with the microbiota gut flora in T1D onset and progression. 1. Introduction Antigen presenting cells activate na£¿ve T lymphocytes by presenting specific antigens, and by providing the necessary costimulatory signals and cytokine environment [1]. T lymphocytes bearing T cell receptor (TCR) specificity towards the presented antigen subsequently undergo clonal expansion and mediate effector functions largely dictated by the stimulatory and environmental clues provided [2]. In a past classical model, CD4+ effector T cells were assigned to either the Th1 or Th2 subset, each with its own distinct cytokines, transcription factors, and functions [3]. Th1 cells produce IFN¦Ã and are regulated by IL-12 through the transcription factor Tbet, while Th2 cells produce the cytokines IL-4, IL-5, and IL-13 and are regulated by the transcription factor GATA3. Th1 cells are associated with protection against intracellular pathogens, and T lymphocytes bearing the Th2 phenotype regulate humoral immunity, and are involved in the protection against extracellular pathogens [4]. Having established a role for Th1 and Th2 cells within the context of immune defense against microorganisms, the Th1/Th2 paradigm was then utilized to garner insight into the onset and progression of autoimmune disorders. The goal of this review is to explicate how limitations of the Th1/Th2 paradigm in the context of autoimmunity led to the discovery of the Th17 phenotype, and to examine the implications of the Th17 phenotype within the context of several autoimmune disorders, including T1D. 2. A Shift in Focus to the Th17 Phenotype The experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) provided the first clues to the possibility that other T cell effector functions, beyond those attributed to the Th1 and Th2 subsets, could be contributing to the onset and progression of autoimmune disorders. Under the
%U http://www.hindawi.com/journals/jir/2013/986789/