Endogenous IL-33 Is Highly Expressed in Mouse Epithelial Barrier Tissues, Lymphoid Organs, Brain, Embryos, and Inflamed Tissues: In Situ Analysis Using a Novel Il-33–LacZ Gene Trap Reporter Strain

  title={Endogenous IL-33 Is Highly Expressed in Mouse Epithelial Barrier Tissues, Lymphoid Organs, Brain, Embryos, and Inflamed Tissues: In Situ Analysis Using a Novel Il-33–LacZ Gene Trap Reporter Strain},
  author={M{\'e}lanie Pichery and Emilie Mirey and Pascale Mercier and Emma Lefrançais and Arnaud Dujardin and Nathalie Ort{\'e}ga and Jean-Philippe Girard},
  journal={The Journal of Immunology},
  pages={3488 - 3495}
IL-33 (previously known as NF from high endothelial venules) is an IL-1 family cytokine that signals through the ST2 receptor and drives cytokine production in mast cells, basophils, eosinophils, invariant NKT and NK cells, Th2 lymphocytes, and type 2 innate immune cells (natural helper cells, nuocytes, and innate helper 2 cells). Little is known about endogenous IL-33; for instance, the cellular sources of IL-33 in mouse tissues have not yet been defined. In this study, we generated an Il-33… 

Figures from this paper

Regulation of IL-33 by Oncostatin M in Mouse Lung Epithelial Cells

Results indicate Oncostatin M as a potent inducer of IL-33 in mouse lung epithelial cells and suggest that an OSM/IL-33 axis may participate in innate immunity and inflammatory conditions in lung.

IL-33–Stimulated Murine Mast Cells Polarize Alternatively Activated Macrophages, Which Suppress T Cells That Mediate Experimental Autoimmune Encephalomyelitis

The findings reveal that IL-33 can promote immunosuppressive responses by polarizing AAMΦ via mast cell–derived IL-6 and IL-13 and attenuated the encephalitogenic function of T cells in the experimental autoimmune encephalomyelitis model.

IL‐33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells

The findings show that IL‐33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC‐mediated pathway.

Extracellular IL-33 cytokine, but not endogenous nuclear IL-33, regulates protein expression in endothelial cells

It is found that exogenous extracellular IL-33 cytokine induced expression of a distinct set of proteins associated with inflammatory responses in endothelial cells, and knockdown of endogenous nuclear IL- 33 expression using two independent RNA silencing strategies had no reproducible effect on the endothelial cell proteome.

Interleukin‐33 (IL‐33): A nuclear cytokine from the IL‐1 family

15 years of discoveries on IL‐33 protein are highlighted, including its molecular characteristics, nuclear localization, bioactive forms, cellular sources, mechanisms of release and regulation by proteases, and important roles in allergic, fibrotic, infectious, and chronic inflammatory diseases.

Fibroblast‐derived IL‐33 is dispensable for lymph node homeostasis but critical for CD8 T‐cell responses to acute and chronic viral infection

FRC is identified as key IL‐33 source driving acute and chronic antiviral T‐cell responses, and findings show that LN T‐zone FRC not only regulates the homeostasis of naïve T cells but also their expansion and differentiation several days into an antiviral response.

Stromal cells maintain immune cell homeostasis in adipose tissue via production of interleukin-33

It is shown that WAT-resident mesenchyme-derived stromal cells are the dominant producers of IL-33, revealing a previously unrecognized regulatory network between tissue-resident progenitor cells and innate lymphoid cells that maintains immune homeostasis in adipose tissue.

IL-33 Receptor-Expressing Regulatory T Cells Are Highly Activated, Th2 Biased and Suppress CD4 T Cell Proliferation through IL-10 and TGFβ Release

It is reported that ST2 expression identifies a highly activated, strongly suppressive Treg subset preferentially located in non-lymphoid tissues, and may be well positioned to immediately react to IL-33 alarm signals.



The IL-1-Like Cytokine IL-33 Is Constitutively Expressed in the Nucleus of Endothelial Cells and Epithelial Cells In Vivo: A Novel ‘Alarmin’?

It is speculated that IL-33 may function, similarly to the prototype ‘alarmin’ HMGB1, as an endogenous ‘danger’ signal to alert the immune system after endothelial or epithelial cell damage during trauma or infection.

Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

A critical role for lung ILCs in restoring airway epithelial integrity and tissue homeostasis after infection with influenza virus is demonstrated.

Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation.

It is shown that nuclear IL-33 is expressed in blood vessels of healthy tissues but down-regulated at the earliest onset of angiogenesis during wound healing; in addition, it is almost undetectable in human tumor vessels and it is speculated that the proposed transcriptional repressor function of IL- 33 may be involved in the control of endothelial cell activation.

Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation.

It is demonstrated that intra-nasal administration of IL-33 triggered an immediate allergic response in the airways, and more importantly, it is shown that endogenousIL-33 contributes to airway inflammation and peripheral antigen-specific responses in ovalbumin-induced acute allergic lung inflammation using IL- 33-deficient mice.

Coexpression of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse.

It is proposed that ELC- and SLC-expressing T zone stromal cells play a central role in bringing naive T cells and DCs together for the initiation of immune responses.

Systemically dispersed innate IL-13–expressing cells in type 2 immunity

Type 2 immunity is a stereotyped host response to allergens and parasitic helminths that is sustained in large part by the cytokines IL-4 and IL-13. Recent advances have called attention to the

IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells.

Results indicate that in addition to its activity on human mast cells, IL-33 is capable of activating human basophils, polarized T cells, iNKT and NK cells, and the nature of the responses elicited by IL- 33 suggests that this axis may amplify both T(h)1- and T( h)2-oriented immune responses.

Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33.

It is demonstrated that basophils and eosinophils are the only direct target leukocytes for IL- 33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system.

Induction of IL‐33 expression and activity in central nervous system glia

It is demonstrated that pathogen‐associated molecular patterns (PAMPs) significantly increase IL‐33 mRNA and protein expression in CNS glia, and this results implicate IL‐ 33‐producing astrocytes as a potentially critical regulator of innate immune responses in the CNS.