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Comment
. 2021 Jul;18(7):1641-1643.
doi: 10.1038/s41423-021-00712-w. Epub 2021 Jun 7.

The two faces of IL-2: a key driver of CD8+ T-cell exhaustion

Byungsuk Kwon  1
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Comment

The two faces of IL-2: a key driver of CD8+ T-cell exhaustion

Byungsuk Kwon. Cell Mol Immunol. 2021 Jul.
No abstract available

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Conflict of interest statement

The author declares no competing interests.

Figures

Fig. 1
Fig. 1. IL-2 is essential for CD8+ T cell exhaustion within tumors.
A At the early stage of tumor growth, IL-2 induces the differentiation of effector CD8+ T cells in an autocrine manner. These CD8+ T cells kill cancer cells and curb tumor growth. B At the later stage of tumor growth, IL-2, which is continually produced by CD4+ T cells, acts on CD8+ T cells to promote their exhaustion. As a consequence, tumor growth is not restrained. C IL-2 signaling in CD8+ T cells results in the phosphorylation of STAT5 through JAK1 and JAK3. Phosphorylated STAT5 forms a dimer that migrates into the nucleus for transcriptional activation of Tph1 expression. The TPH1 enzyme metabolizes Trp to 5-HTP, which then binds AHR. Ligand-bound AHR functions as a transcription factor for IR genes but represses the transcription of Tnf and Ifng. On the other hand, IL-2 signaling is linked to the SUMOylation of AHR, which prevents its degradation by ubiquitination by an unknown mechanism (a mechanistic diagram is omitted). AHR aryl hydrocarbon receptor, 5-HTP 5-hydroxytryptophan, IR inhibitory receptor, JAK Janus kinase, STAT5 signal transducer and activator of transcription 5, TPH1 tryptophan hydroxylase 1, Trp tryptophan.
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