T helper 17 cell heterogeneity and pathogenicity in autoimmune disease

Kamran Ghoreschi; Arian Laurence; Xiang-Ping Yang; Kiyoshi Hirahara; John J O'Shea

doi:10.1016/j.it.2011.06.007

T helper 17 cell heterogeneity and pathogenicity in autoimmune disease

Trends Immunol. 2011 Sep;32(9):395-401. doi: 10.1016/j.it.2011.06.007. Epub 2011 Jul 23.

Authors

Kamran Ghoreschi¹, Arian Laurence, Xiang-Ping Yang, Kiyoshi Hirahara, John J O'Shea

Affiliation

¹ Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.

Abstract

T helper (Th)17 cells have been proposed to represent a new CD4(+) T cell lineage that is important for host defense against fungi and extracellular bacteria, and the development of autoimmune diseases. Precisely how these cells arise has been the subject of some debate, with apparent species-specific differences in mice and humans. Here, we describe evolving views of Th17 specification, highlighting the contribution of transforming growth factor-β and the opposing roles of signal transducer and activator of transcription (STAT)3 and STAT5. Increasing evidence points to heterogeneity and inherent phenotypic instability in this subset. Ideally, better understanding of expression and action of key transcription factors and the epigenetic landscape of Th17 can help explain the flexibility and diversity of interleukin-17-producing cells.

Publication types

Review

MeSH terms

Animals
Autoimmune Diseases / pathology*
Autoimmune Diseases / physiopathology
Bacterial Infections / immunology*
Bacterial Infections / microbiology
Cell Differentiation / genetics
Cell Differentiation / immunology
Cell Lineage / immunology
Genetic Variation / immunology
Humans
Immunity, Cellular* / genetics
Interleukin-17 / biosynthesis
Interleukin-17 / immunology*
Interleukin-23 Subunit p19 / biosynthesis
Interleukin-23 Subunit p19 / immunology*
Mice
Mycoses / immunology*
Mycoses / microbiology
Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
STAT3 Transcription Factor / immunology
STAT3 Transcription Factor / metabolism
STAT5 Transcription Factor / immunology
STAT5 Transcription Factor / metabolism
Signal Transduction / immunology
Species Specificity
Th17 Cells* / cytology
Th17 Cells* / immunology
Th17 Cells* / metabolism
Transforming Growth Factor beta / immunology
Transforming Growth Factor beta / metabolism

Substances

Il23a protein, mouse
Interleukin-17
Interleukin-23 Subunit p19
Nuclear Receptor Subfamily 1, Group F, Member 3
STAT3 Transcription Factor
STAT5 Transcription Factor
Transforming Growth Factor beta

Grants and funding

Z99 AR999999/Intramural NIH HHS/United States