Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Nov 15;25(4):305-12.
doi: 10.1016/j.smim.2013.10.009. Epub 2013 Nov 5.

The plasticity of human Treg and Th17 cells and its role in autoimmunity

Markus Kleinewietfeld  1 , David A Hafler
Affiliations
Review

The plasticity of human Treg and Th17 cells and its role in autoimmunity

Markus Kleinewietfeld et al. Semin Immunol. .

Abstract

CD4(+) T helper cells are a central element of the adaptive immune system. They protect the organism against a wide range of pathogens and are able to initiate and control many immune reactions in combination with other cells of the adaptive and the innate immune system. Starting from a naive cell, CD4(+) T cells can differentiate into various effector cell populations with specialized function. This subset specific differentiation depends on numerous signals and the strength of stimulation. However, recent data have shown that differentiated CD4(+) T cell subpopulations display a high grade of plasticity and that their initial differentiation is not an endpoint of T cell development. In particular, FoxP3(+) regulatory T cells (Treg) and Th17 effector T cells demonstrate a high grade of plasticity, which allow a functional adaptation to various physiological situations during an immune response. However, the plasticity of Treg and Th17 cells might also be a critical factor for autoimmune disease. Here we discuss the recent developments in CD4(+) T cell plasticity with a focus on Treg and Th17 cells and its role in human autoimmune disease, in particular multiple sclerosis (MS).

Keywords: Autoimmunity; CD4(+) T cells; FoxP3; IL-17; T cell plasticity; Th17; Treg.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Plasticity of Treg and Th17 cells
Indicated are the major routes of human Treg and Th17 plasticity. Danger signals like extracellular ATP or microbial stimuli can induce cytokine release (e.g. IL-1β) by antigen presenting cells (APC). FoxP3+ Tregs can inhibit this process for instance through CD39-mediated hydrolysis of extracellular ATP. Tregs can be induced by IL-12 to become pro-inflammatory IFN-γ producing cells, expressing TBX21 and CXCR3, which loose suppressive capacity while retaining FoxP3 expression (Th1 Treg). In the presence of IL-1β and IL-6 Tregs can acquire a Th17-like phenotype. These cells secrete IL-17 and express RORc, high levels of CCR6 and CD161 but can retain suppressive capacity and FoxP3 expression (Th17 Treg). Highly pathogenic Th17 cells start to express IFN-γ and upregulate TBX21 and CXCR3 in the presence of IL-12 or of IL-1β when primed by C.albicans (indicated by the dotted line) but retain expression of CCR6 and CD161 (Th1 Th17). Th17 cells can also convert into anti-inflammatory IL-4 or IL-10 expressing CD161+ CCR6+ Th17 cells in the presence of IL-4 or when primed by S.aureus. Additionally, a similar phenotype was observed when Th17 cells were redirected to the small intestine (Th2 Th17).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annual review of immunology. 2009;27:485–517. - PubMed
    1. Vahedi G, ACP, Hand TW, Laurence A, Kanno Y, O’Shea JJ, et al. Helper T-cell identity and evolution of differential transcriptomes and epigenomes. Immunological reviews. 2013;252:24–40. - PMC - PubMed
    1. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–787. - PubMed
    1. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nature immunology. 2005;6:1133–1141. - PMC - PubMed
    1. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature immunology. 2005;6:1123–1132. - PubMed

Publication types

MeSH terms