ArticleJournal of immunology (Baltimore, Md. : 1950)2014
IL-33 is an unconventional Alarmin that stimulates IL-2 secretion by dendritic cells to selectively expand IL-33R/ST2+ regulatory T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 209 citations in OpenAlex.
- IL-33/IL1RL1 (ST2) signalling drives immune suppression in squamous intraepithelial hyperplasia.Tumour virus research · 2026Article
- Rewiring Atopic Dermatitis: Alarmin Cytokines at the Core of Barrier-Immune-Neuro-Microbiome Networks.Clinical reviews in allergy & immunology · 2026Review
- Decoding TNF receptor superfamily control of CD4Cell communication and signaling : CCS · 2026Review
- Regulatory T cells in stroke inflammation: Therapeutic perspectives.Neural regeneration research · 2026Article
- Nomogram based on serum interleukin-33 levels and clinical characteristics for predicting overall survival in hematologic malignancy patients receiving haplo-HDPSCT.Annals of hematology · 2026Article
- Cytokines Associated with Activation of CD4International journal of molecular sciences · 2026Review
- Restoring B cell intrinsic tolerance to lupus autoimmunity: a rational strategy for lupus treatment.Frontiers in immunology · 2026Review
- Critical role of interleukin-33 in pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease.Frontiers in medicine · 2026Review
- Functional Specialization and Collaboration of cDC2 Subsets in CD4+ T Cell Priming and Differentiation.Immunological reviews · 2025Review
- Activity-attenuated serum albumin-fused interleukin-33 suppresses experimental autoimmune encephalomyelitis.Cell reports. Medicine · 2025Article
- The role of IL-2 in type 2 immunity.Frontiers in immunology · 2025Review
- Spleen and peripheral blood immunopathology in an outbred model of adult-stage murine schistosomiasis.Frontiers in immunology · 2025Article
- Epithelial-derived cytokines in the pathogenesis of severe asthma.Frontiers in allergy · 2025Review
- Dynamics of tissue repair regulatory T cells and damage in acute Trypanosoma cruzi infection.PLoS pathogens · 2025Article
- HMOS 2'FL and 3FL prevent house dust mite induced proinflammatory cytokine releaseFrontiers in nutrition · 2025Article
- Studies of Structure-Activity Relationship of 2-(Pyrrolidin-1ylmethyl)-1ACS medicinal chemistry letters · 2024Article
- IL-33: Friend or foe in transplantation?The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Review
- IL-33 and IL-33-derived DC-based tumor immunotherapy.Experimental & molecular medicine · 2024Review
- Deciphering the developmental trajectory of tissue-resident Foxp3Frontiers in immunology · 2024Review
- The impact of regulatory T cells on the graft-versus-leukemia effect.Frontiers in immunology · 2024Review
76 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
IL-33 is a recently characterized IL-1 family member that is proposed to function as an alarmin, or endogenous signal of cellular damage, as well as act as a pleiotropic cytokine. The ability of IL-33 to potentiate both Th1 and Th2 immunity supports its role in pathogen clearance and disease immunopathology. Yet, IL-33 restrains experimental colitis and transplant rejection by expanding regulatory T cells (Treg) via an undefined mechanism. We sought to determine the influence of IL-33 on hematopoietic cells that drives Treg expansion and underlies the therapeutic benefit of IL-33 administration. In this study, we identify a feedback loop in which conventional mouse CD11c(+) dendritic cells (DC) stimulated by IL-33 secrete IL-2 to selectively expand IL-33R(ST2(+))- suppressive CD4(+)Foxp3(+) Treg. Interestingly, this occurs in the absence of classical DC maturation, and DC-derived (innate) IL-2 increases ST2 expression on both DC and interacting Treg. ST2(+) Treg represent an activated subset of Foxp3(+) cells, demonstrated to be ICOS(high)CD44(high) compared with their ST2(-) counterparts. Furthermore, although studies have shown that IL-33-exposed DC promote Th2 responses, we reveal that ST2(+) DC are required for IL-33-mediated in vitro and in vivo Treg expansion. Thus, we have uncovered a relationship between IL-33 and innate IL-2 that promotes the selective expansion of ST2(+) Treg over non-Treg. These findings identify a novel regulatory pathway driven by IL-33 in immune cells that may be harnessed for therapeutic benefit or for robust expansion of Treg in vitro and in vivo.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.