Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction

By Kojiro Sato, Ayako Suematsu, Kazuo Okamoto, A. Yamaguchi, Y. Morishita, Y. Kadono, Sakae Tanaka, T. Kodama, Shizuo Akira, Y. Iwakura and 2 more. Journal of Experimental Medicine, 2006

1,580 citations recorded by the source corpus.

In autoimmune arthritis, traditionally classified as a T helper (Th) type 1 disease, the activation of T cells results in bone destruction mediated by osteoclasts, but how T cells enhance osteoclastogenesis despite the anti-osteoclastogenic effect of interferon (IFN)-γ remains to be elucidated. Here, we examine the effect of various Th cell subsets on osteoclastogenesis and identify Th17, a specialized inflammatory subset, as an osteoclastogenic Th cell subset that links T cell activation and bone resorption. The interleukin (IL)-23–IL-17 axis, rather than the IL-12–IFN-γ axis, is critical not only for the onset phase, but also for the bone destruction phase of autoimmune arthritis. Thus, Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/1460afec4acd11275cb2ff03071dbdd2e8a2d7b8

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In Molecular Biology

1. F. Bäckhed
2. V. Tremaroli
3. Georg Schett
4. F. Nimmerjahn
5. Rob Knight

In Oncology

1. Georg Schett
2. F. Bäckhed
3. F. Nimmerjahn
4. S. Gaffen

Citations in the corpus

• Cancer to bone: a fatal attraction (2011, neutral): “Of note, pro-inflammatory CD4 + T H 17 cells secrete RANKL, tumour necrosis factor (TNF) and TGFβ, all of which activate osteoclasts and promote bone resorptio”
• The gut microbiota regulates bone mass in mice (2012, background): “Of these, Th17 cells are osteoclastogenic and suggested to be responsible for the bone destruction phase of autoimmune arthritis.((18)) GF mice have been shown to have a Th2-skewed profile with increased production of IL-4 and decreased production of IFNg from splenic CD4þ T cells in vitro.”
• Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. (2012, positive): “T cell activation, particularly that of the proinflammatory TH17 subset, fosters the expression of RANKL and induces osteo-clastogenesis (23).”
• A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage (2007, background): “T H 1 plays a protective role in bone metabolism, while T H 17 is destructiv”