Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8<sup>+</sup>T Cells, Resulting in Enhanced IL-1β Dependent Effector Function

Kim, Dong Hyun; Kim, Hee Young; Lee, Won Woo

doi:10.4110/in.2021.21.e33

Cited by 4 publications

(3 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed a different set of predicted chemokine-chemokine receptor interactions in health vs CD, with CCL3 , CCL4 , and CCL5 being more prominent in health and CXCL8 and CXCL16 being more prominent in patients with CD (Figure 3 a). Moreover, in patients with CD, IL1B produced by myeloid dendritic cells was predicted to bind to its receptor IL1R1 on CD8 + T EM cells (Figure 3 a, right); IL-1β–mediated signaling in CD8 + T cells has been reported to increase effector functions such as production of inflammatory cytokines and granzyme B ( 29 ). Examination of previously published gene expression data from patients with CD ( 12 ) confirmed that certain T-cell subsets expressed detectable levels of IL1R1 (see Supplementary Figure 2A, http://links.lww.com/CTG/A923 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of CD8+ T cell - immune cell communications in ileal Crohn’s disease

Duong

Choi

Hsu

et al. 2023

Clin Transl Gastroenterol

View full text Add to dashboard Cite

INTRODUCTION: Crohn's disease (CD) is a major subtype of inflammatory bowel disease (IBD), a spectrum of chronic intestinal disorders caused by dysregulated immune responses to gut microbiota. Although transcriptional and functional changes in a number of immune cell types have been implicated in the pathogenesis of IBD, the cellular interactions and signals that drive these changes have been less well-studied. METHODS: We performed Cellular Indexing of Transcriptomes and Epitopes by sequencing on peripheral blood, colon, and ileal immune cells derived from healthy subjects and patients with CD. We applied a previously published computational approach, NicheNet, to predict immune cell types interacting with CD8+ T-cell subsets, revealing putative ligand-receptor pairs and key transcriptional changes downstream of these cell-cell communications. RESULTS: As a number of recent studies have revealed a potential role for CD8+ T-cell subsets in the pathogenesis of IBD, we focused our analyses on identifying the interactions of CD8+ T-cell subsets with other immune cells in the intestinal tissue microenvironment. We identified ligands and signaling pathways that have implicated in IBD, such as interleukin-1β, supporting the validity of the approach, along with unexpected ligands, such as granzyme B, which may play previously unappreciated roles in IBD. DISCUSSION: Overall, these findings suggest that future efforts focused on elucidating cell-cell communications among immune and nonimmune cell types may further our understanding of IBD pathogenesis.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of CD8+ T cell - immune cell communications in ileal Crohn’s disease

Duong

Choi

Hsu

et al. 2023

Clin Transl Gastroenterol

View full text Add to dashboard Cite

show abstract

“…We hypothesize that, in this way, newly primed and activated CD8 Teff cells are prepared to operate better in environments that are enriched in IL-1 cytokines during active pathogen infection. Such a mechanism might also be in play beyond the context of CD8 T cell priming, as a recent work by Kim et al demonstrated that IL-1R1 expression can be increased in activated human CD8 T cells via CD4 T cells that secrete IL-21 [24].…”

Section: Discussionmentioning

confidence: 99%

Rethinking IL-1 Antagonism in Respiratory Viral Infections: A Role for IL-1 Signaling in the Development of Antiviral T Cell Immunity

Van Den Eeckhout,

Ballegeer,

De Clercq

et al. 2023

IJMS

View full text Add to dashboard Cite

IL-1R integrates signals from IL-1α and IL-1β, and it is widely expressed across tissues and immune cell types. While the expression pattern and function of IL-1R within the innate immune system is well studied, its role in adaptive immunity, particularly within the CD8 T cell compartment, remains underexplored. Here, we show that CD8 T cells dynamically upregulate IL-1R1 levels during priming by APCs, which correlates with their proliferation status and the acquisition of an effector phenotype. Notably, this IL-1 sensitivity persists in memory CD8 T cells of both mice and humans, influencing effector cytokine production upon TCR reactivation. Furthermore, our study highlights that antiviral effector and tissue-resident CD8 T cell responses against influenza A virus infection become impaired in the absence of IL-1 signaling. Altogether, these data support the exploitation of IL-1 activity in the context of T cell vaccination strategies and warrant consideration of the impact of clinical IL-1 inhibition on the rollout of T cell immunity.

show abstract

“…Interestingly, IL-21 can have a pro-apoptotic effect on B-cells in the absence of co-stimulation, making IL-21 important for the prevention of autoreactive antibody production. IL-21 can further promote the expansion of CD8 memory T-cells in the presence of IL-7 or IL-15, improves NK cell viability and function, memory T-cell persistence and cytotoxic CD8 T-cell function ( 6 96 ). Notably, IL-21 does not promote Treg differentiation, although the presence of Tregs can mitigate the IL-21-induced expansion of CD8 T-cells ( 97 ).…”

Section: Il-21mentioning

confidence: 99%

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

Wolfarth¹,

Dhar²,

Goon³

et al. 2022

Immune Netw

View full text Add to dashboard Cite

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short half-life of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

show abstract

Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8⁺T Cells, Resulting in Enhanced IL-1β Dependent Effector Function

Cited by 4 publications

References 65 publications

Identification of CD8+ T cell - immune cell communications in ileal Crohn’s disease

Identification of CD8+ T cell - immune cell communications in ileal Crohn’s disease

Rethinking IL-1 Antagonism in Respiratory Viral Infections: A Role for IL-1 Signaling in the Development of Antiviral T Cell Immunity

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

Contact Info

Product

Resources

About

Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8+T Cells, Resulting in Enhanced IL-1β Dependent Effector Function

Cited by 4 publications

References 65 publications

Identification of CD8+ T cell - immune cell communications in ileal Crohn’s disease

Identification of CD8+ T cell - immune cell communications in ileal Crohn’s disease

Rethinking IL-1 Antagonism in Respiratory Viral Infections: A Role for IL-1 Signaling in the Development of Antiviral T Cell Immunity

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

Contact Info

Product

Resources

About

Induction of Unique STAT Heterodimers by IL-21 Provokes IL-1RI Expression on CD8⁺T Cells, Resulting in Enhanced IL-1β Dependent Effector Function