Emerging Roles of IL-33/ST2 Axis in Renal Diseases

Chen, Wei‐Yu; Li, Lung-Chih; Yang, Jenq-Lin

doi:10.3390/ijms18040783

Cited by 53 publications

(42 citation statements)

References 105 publications

(162 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-33 is mainly and constitutively expressed in the nuclei of epithelial barrier tissues and endothelial cells, and it can, therefore, be immediately released in response to cell injury. The few studies on the cellular localization of IL-33 in the kidney have documented a constitutive expression in endothelial nuclei of renal large and small vessels in humans 42 and also, peritubular vascular endothelial cells with a similar expression profile 21,23 in mice. In agreement with these data, we show here that, in healthy murine kidneys, IL-33 is mainly expressed by CD31(+) CD45(2) endothelial cells in peritubular capillaries and CD31(2) CD45(2) interstitial cells, which may be pericytes, endothelial progenitor cells, and/ or fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Endogenous IL-33 Contributes to Kidney Ischemia-Reperfusion Injury as an Alarmin

Ferhat¹,

Robin²,

Giraud³

et al. 2018

JASN

View full text Add to dashboard Cite

Inflammation is a prominent feature of ischemia-reperfusion injury (IRI), which is characterized by leukocyte infiltration and renal tubular injury. However, signals that initiate these events remain poorly understood. We examined the role of the nuclear alarmin IL-33 in tissue injury and innate immune response triggered by experimental kidney ischemia-reperfusion. In wild-type mice, we found that IL-33 was constitutively expressed throughout the kidney in peritubular and periglomerular spaces, mainly by microvascular endothelial cells, from which it was released immediately during IRI. Compared with wild-type mice, mice lacking IL-33 (IL-33) exhibited reductions in early tubular cell injury and subsequent renal infiltration of IFN-/IL-17A-producing neutrophils, with preservation of renal functions. This protection associated with decreased renal recruitment of myeloid dendritic cells, natural killer (NK) cells, and invariant natural killer T (iNKT) cells, the latter of which were reported as deleterious in IRI. Increases in the level of circulating IL-12, a key IL-33 cofactor, and the expression of ST2, an IL-33-specific receptor, on the surface of iNKT cells preceded the IL-33- and iNKT cell-dependent phase of neutrophil infiltration. Furthermore, IL-33 directly targeted iNKT cells , inducing IFN- and IL-17A production. We propose that endogenous IL-33 is released as an alarmin and contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, resulting in neutrophil infiltration and activation at the injury site. Our findings show a novel molecular mediator contributing to innate immune cell recruitment induced by renal ischemia-reperfusion and may provide therapeutic insights into AKI associated with renal transplantation.

show abstract

Section: Discussionmentioning

confidence: 99%

Endogenous IL-33 Contributes to Kidney Ischemia-Reperfusion Injury as an Alarmin

Ferhat¹,

Robin²,

Giraud³

et al. 2018

JASN

View full text Add to dashboard Cite

show abstract

“…Recently, several studies have suggested that IL-33 is involved in the pathogenesis of kidney diseases and the associated tissue reparative responses [17,18]. For example, IL-33 level had increased in unilateral urinary obstruction (UUO) model in mice [19].…”

Section: Introductionmentioning

confidence: 99%

Emerging Roles of Interleukin-33-responsive Kidney Group 2 Innate Lymphoid Cells in Acute Kidney Injury

Chen

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses. IL-33 triggers pleiotropic immune functions in multiple types of immune cells, which express the IL-33 receptor, ST2. Recent studies have revealed the potential applications of IL-33 for treating acute kidney injury in preclinical animal models. However, IL-33 and IL-33-responding immune cells are reported to exhibit both detrimental and beneficial roles. The IL-33-mediated immunomodulatory functions have been investigated using loss-of-function approaches, such as IL33-deficient mice, IL-33 antagonists, or administration of exogenous IL-33 recombinant protein. This review will discuss the key findings on IL-33-mediated activation of kidney resident group 2 innate lymphoid cells (ILC2s) and summarize the current understanding of the differential functions of endogenous IL-33 and exogenous IL-33 and their potential implications in treating acute kidney injury.

show abstract

“…Unlike ST2L, sST2 lacks the transmembrane and cytoplasmic domains. sST2 has been associated with several diseases such as bronchial asthma, heart failure (HF), arthritis, sepsis in trauma patients, central nervous system (CNS) diseases, liver diseases and renal diseases . sST2 has been shown to be an efficient prognostic marker for patients with chronic HF .…”

Section: Introductionmentioning

confidence: 99%

“…sST2 has been associated with several diseases such as bronchial asthma, heart failure (HF), arthritis, sepsis in trauma patients, central nervous system (CNS) diseases, liver diseases and renal diseases. [6][7][8][9][10][11][12] sST2 has been shown to be an efficient prognostic marker for patients with chronic HF. 13 In spite of a large amount of data gathered in last decade for different biomarkers and their prognostic capacity, there are few studies that have assessed their effectiveness in ACS along with chronic noncardiovascular comorbidities.…”

Section: Introductionmentioning

confidence: 99%