Yonsei Med J.  2019 Feb;60(2):126-131. 10.3349/ymj.2019.60.2.126.

Tumor Necrosis Factor and Regulatory T Cells

• Jung MK
• Lee JS
• Kwak JE
• Shin EC

• KMID: 2431628
• DOI: http://doi.org/10.3349/ymj.2019.60.2.126

Abstract

CD4⁺CD25⁺FoxP3⁺ regulatory T (Treg) cells play major roles in the maintenance of immune homeostasis. In this review, we comprehensively describe the relationship between tumor necrosis factor (TNF) and Treg cells, focusing on the effects of TNF on Treg cells and on TNF-producing Treg cells. Contradictory results have been reported for the effect of TNF on the suppressive activity of Treg cells. In patients with rheumatoid arthritis, TNF has been shown to reduce the suppressive activity of Treg cells. Meanwhile, however, TNF has also been reported to maintain the suppressive activity of Treg cells via a TNFR2-mediated mechanism. In addition, Treg cells have been found to acquire the ability to produce TNF under inflammatory conditions, such as acute viral hepatitis. These TNF-producing Treg cells exhibit T helper 17-like features and hold significance in various human diseases.

Keyword

Tumor necrosis factor; regulatory T cell; inflammation; TNFR2

MeSH Terms

Arthritis, Rheumatoid
Hepatitis
Homeostasis
Humans
Inflammation
Receptors, Tumor Necrosis Factor, Type II
T-Lymphocytes, Regulatory*
Tumor Necrosis Factor-alpha*
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 TNF-producing Treg cells in AHA patients. Treg cells from AHA patients produce TNF and exhibit reduced suppressive activity due to inflammatory conversion. In AHA patients, TNF-producing Treg cells are associated with severe liver injury mediated by immunopathologic mechanisms. Two possible mechanisms have been proposed to explain how TNF-producing Treg cells are involved in liver injury. (A) First, the reduced suppressive activity of TNF-producing Treg cells may lead to unchecked activation of effector T cells, which contributes to liver injury. (B) Second, TNF produced by Treg cells may directly contribute to liver injury. The magnified figure on the right shows the phenotypic characteristics of TNF-producing Treg cells. TNF, tumor necrosis factor; AHA, acute hepatitis A; Treg, regulatory T.

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