Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of interleukin-2 receptor signaling

Moro, Alejandro; Wang, Lily; Yu, Aixin; Hsiung, Sunnie; Ban, Yuguang; Yan, Aimin; Sologon, Corneliu; Chen, X Steven; Malek, Thomas R.

doi:10.1038/s41590-022-01179-1

Cited by 16 publications

(14 citation statements)

References 58 publications

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“…Indeed, enrichment analysis showed that Myc targets were very highly represented in Cluster 5 (297 genes, P < 10 −138 ), indicating that Myc is the major driver of this response. Thus, consistent with early work (Rapp et al, 1985;Miyazaki et al, 1995;Klemsz et al, 1989;Moro et al, 2022;Marchingo et al, 2020) and downstream transcriptional regulators (STAT2, Batf), with "response to stimulus" as a main ontology term (Fig. 2 B, 51 genes, FDR = 0.006).…”

Section: Resultssupporting

confidence: 89%

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages

Baysoy

Seddu

Salloum

et al. 2023

Journal of Experimental Medicine

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“γc” cytokines are a family whose receptors share a “common-gamma-chain” signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine. Responses include a major downregulation component and a broad Myc-controlled resetting of biosynthetic and metabolic pathways. Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises were uncovered: IL2 effects in mast cells, shifts between follicular and marginal zone B cells, paradoxical and cell-specific cross-talk between interferon and γc signatures, or an NKT-like program induced by IL21 in CD8+ T cells.

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Section: Resultssupporting

confidence: 89%

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages

Baysoy

Seddu

Salloum

et al. 2023

Journal of Experimental Medicine

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“…IL2R-deficient mice could result in the absence of functional Tregs, while transfer of limited numbers of Tregs could prevent autoimmune disease. 42 IL7R is a promising candidate for autoimmunity due to its involvement in the regulation of the Tregs homeostasis, proliferation, and anti-apoptotic signaling. 43 While its downregulation might induce Tregs more sensitivity to apoptosis stimuli.…”

Section: Resultsmentioning

confidence: 99%

Elevated apoptosis and abnormal apoptosis signaling of regulatory T cells in patients with systemic lupus erythematosus

et al. 2022

Lupus

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In systemic lupus erythematosus (SLE), immune tolerance is influenced by defects in naturally occurring T cells (Tregs). To investigate the apoptosis rate of Tregs and their suppressive activity in patients with SLE and then to recognize the genes and signaling pathways that cause Treg apoptosis. FACS was used to assess the frequency and apoptosis rates of Tregs in 48 SLE patients and 28 normal controls (NCs). Coculture of Tregs with CD4+CD25−CD127dim/− T cells was used to assess the suppressive activity of Tregs. Microarray analysis was used to generate unstimulated Tregs gene expression profiles from very high activity patients with SLE and NCs. Real-time PCR was used to confirm differential gene expression. In patients with SLE, the frequency of Tregs was substantially reduced compared to Tregs from NCs. Furthermore, Tregs from SLE patients had an elevated rate of apoptosis and a lower suppressing ability than Tregs from NCs. Tregs apoptosis was negatively associated with the total count of Tregs and positively related to disease activity. Unstimulated Tregs gene expression profiles from patients with recent-onset SLE revealed a biological response that can cause apoptosis, partially triggered by stress, DNA damage, and cytokine stimulation. The discovery of pathway-specific expression signatures is a significant step forward in understanding how Tregs defects contribute to the pathogenesis of SLE. Our findings may contribute to the development of new strategies for treating SLE based on abnormal Tregs apoptosis and restoring immune homeostasis in patients with SLE.

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“… 170 , 171 IL-2 contributes to the activation and proliferation of Tregs, CTLs and NK cells, as previously described. 172 FoxP3 induces the expression of CD25, a high-affinity receptor for IL-2, suggesting that Tregs may express more CD25 than CTLs and NK cells. Therefore, Tregs may better inhibit the functions and proliferation of T cells and NK cells by preferentially using IL-2.…”

Section: T Cellsmentioning

confidence: 99%

Radiation-induced tumor immune microenvironments and potential targets for combination therapy

Guo

Yao

Tan

et al. 2023

Sig Transduct Target Ther

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As one of the four major means of cancer treatment including surgery, radiotherapy (RT), chemotherapy, immunotherapy, RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery. Although RT is an important modality for cancer treatment, the consequential changes caused by RT in the tumor microenvironment (TME) have not yet been fully elucidated. RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. During RT, alterations in signaling pathways result in changes in the local immune microenvironment. However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. Patients who are radioresistant respond poorly to RT and may experience cancer progression. Given that the emergence of radioresistance is inevitable, new radiosensitization treatments are urgently needed. In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. Overall, this review highlights the possibilities of synergistic therapy by building on existing research.

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Dynamic transcriptional activity and chromatin remodeling of regulatory T cells after varied duration of interleukin-2 receptor signaling

Cited by 16 publications

References 58 publications

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages

The interweaved signatures of common-gamma-chain cytokines across immunologic lineages

Elevated apoptosis and abnormal apoptosis signaling of regulatory T cells in patients with systemic lupus erythematosus

Radiation-induced tumor immune microenvironments and potential targets for combination therapy

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