A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17

Abstract

Interleukin 17 (IL-17) has been linked to autoimmune diseases, although its regulation and function have remained unclear. Here we have evaluated in vitro and in vivo the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. This process required the costimulatory molecules CD28 and ICOS but was independent of the cytokines and transcription factors required for T helper type 1 or type 2 differentiation. Furthermore, both IL-4 and interferon-gamma negatively regulated T helper cell production of IL-17 in the effector phase. In vivo, antibody to IL-17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused chemokine production and leukocyte infiltration. Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation.

Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice

“…This corresponds to the Th1/Th2 paradigm proposed by Mosmann et al [1]. More recently, a third subset of Th cells, Th17 cells, has been described; this is a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells [2,3]. Th17 cells are generally thought to be proinflammatory, especially through the production of IL-17 [2,3].…”

“…More recently, a third subset of Th cells, Th17 cells, has been described; this is a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells [2,3]. Th17 cells are generally thought to be proinflammatory, especially through the production of IL-17 [2,3]. Th17 cells have been shown to participate in the development of autoimmunity, and also to play an important role in host defense against infection [4].…”

Mucosal‐associated invariant T cells in autoimmunity, immune‐mediated diseases and airways disease

“…Asthma is characterized by airways inflammation, classically associated with activated allergen‐specific Th2 cells64 secreting IL‐4, IL‐5 and IL‐13, which orchestrate the function of eosinophils, mast cells and B cells 44, 65. There is increasing recognition of disease heterogeneity and some genetic66, 67 and murine68, 69 data implicating IL‐17 in certain phenotypes of asthma. We conducted a large‐scale bronchoscopy‐based study of 60 patients spanning the spectrum of asthma severity and phenotypes and 24 healthy controls analysing multiple T‐cell subsets in the context of deep clinical and immunological phenotyping 44.…”

TLR2‐activated human langerhans cells promote Th17 polarization via IL‐1β, TGF‐β and IL‐23

“…Recently, Th17 cells are described as a further specialized subset of CD4 1 effector cells in addition to the well-known Th1 and Th2 cells [1][2][3]. Upon stimulation Th17 cells acquire the capacity to produce the inflammatory cytokine IL-17 [4].…”