Editors' ChoiceImmunology

How Treg cells stay true

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Sci. Signal.  22 May 2018:
Vol. 11, Issue 531, eaau2250
DOI: 10.1126/scisignal.aau2250

Human Treg cells maintain their cellular identity through changes in their protein expression signature.

Regulatory T (Treg) cells constitute a FoxP3+ CD4+ T cell subset that controls the activity of effector T cells. Treg cells suppress pathogenic inflammation, prevent autoimmune disease, and promote wound healing. Because Treg cells perform such critical functions, it is vital that they maintain their cellular identity in the face of inflammatory signals that can destabilize FoxP3 expression. Similar to conventional T cells, Treg cells are quite diverse and can be divided into naïve and effector subsets. By comparing the proteomic and transcriptomic signatures of CD4+ Treg and effector T cell subsets in human blood, Cuadrado et al. identified a Treg cell–specific core protein signature that would not have been predicted from the transcriptomics data alone. Furthermore, the authors found that in highly suppressive effector Treg cells, key signaling proteins involved in antigen and inflammatory cytokine sensing were reduced in abundance as compared with those in other CD4+ T cell subsets; specifically, components of nuclear factor κB (NF-κB) and JAK-STAT signaling pathways. Enforced expression of one of these components, the transcription factor STAT4, led to the loss of FoxP3 in Treg cells after T cell receptor activation in the presence of the inflammatory cytokine interferon-α (IFN-α), suggesting that detuning inflammatory signaling may be one way by which Treg cells maintain their identity. Of note, whereas changes in RNA and protein abundance in CD4+ T cell subsets correlated well in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to metabolism and cell division and migration, there was less concordance in both data sets for cell signaling pathways. Overall, this study provides a rich resource for understanding how Treg cells may maintain their cellular identity and underscores the importance of a protein-level analysis of the pathways that cells use to respond to their environment.

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