Stop Press: Eosinophils Drafted to Join the Th17 Team

Keely, Simon; Foster, Paul S.

doi:10.1016/j.immuni.2015.07.010

Cited by 18 publications

(16 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Future studies identifying contrasting regulation of HIF/IL-12/23 responses in innate vs. adaptive cells, are likely to be important. For instance, the recent discovery of a GM-CSF/IL-23 axis that regulates eosinophils in IL-23/Th17 models of colitis 40 may indicate that an imbalance of IL-12/23 could also promote a T helper Type-2 rather than Th17 response, which in the GI tract, may be important in the context of homeostasis, and indeed, eosinophils are important in both IBD 41 and functional GI disorders (FGIDs). 42 In addition, both Th1 and Th17 populations can arise independently of IL-12/IL-23.…”

Section: Discussionmentioning

confidence: 99%

Regulation of IL-12p40 by HIF controls Th1/Th17 responses to prevent mucosal inflammation

et al. 2017

View full text Add to dashboard Cite

Intestinal inflammatory lesions are inherently hypoxic, due to increased metabolic demands created by cellular infiltration and proliferation, and reduced oxygen supply due to vascular damage. Hypoxia stabilizes the transcription factor hypoxia-inducible factor-1α (HIF) leading to a coordinated induction of endogenously protective pathways. We identified IL12B as a HIF-regulated gene and aimed to define how the HIF-IL-12p40 axis influenced intestinal inflammation. Intestinal lamina propria lymphocytes (LPL) were characterized in wild-type and IL-12p40 murine colitis treated with vehicle or HIF-stabilizing prolyl-hydroxylase inhibitors (PHDi). IL12B promoter analysis was performed to examine hypoxia-responsive elements. Immunoblot analysis of murine and human LPL supernatants was performed to characterize the HIF/IL-12p40 signaling axis. We observed selective induction of IL-12p40 following PHDi-treatment, concurrent with suppression of Th1 and Th17 responses in murine colitis models. In the absence of IL-12p40, PHDi-treatment was ineffective. Analysis of the IL12B promoter identified canonical HIF-binding sites. HIF stabilization in LPLs resulted in production of IL-12p40 homodimer which was protective against colitis. The selective induction of IL-12p40 by HIF-1α leads to a suppression of mucosal Th1 and Th17 responses. This HIF-IL12p40 axis may represent an endogenously protective mechanism to limit the progression of chronic inflammation, shifting from pro-inflammatory IL-12p70 to an antagonistic IL-12p40 homodimer.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of IL-12p40 by HIF controls Th1/Th17 responses to prevent mucosal inflammation

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In part, this evidence includes the link between T H 17 cell development and IL-6, a cytokine strongly upregulated in patients with COVID-19 who experience cytokine storm (together with IL-8 induction). Further support comes from the role of IL-17 in promoting the activation, recruitment from bone marrow and extravasation of eosinophils into target organs, such as the lungs 7 , and the finding that alum, an adjuvant that promotes T H 2-type immunity, actually reduces immunopathology 5 . Such observations highlight the potential importance of selecting vaccine delivery platforms and adjuvants that shift host responses away from a T H 17-type immune bias.…”

Section: Cellular Immunopathologymentioning

confidence: 99%

COVID-19 vaccine design: the Janus face of immune enhancement

2020

View full text Add to dashboard Cite

“…and Th17 induction promote eosinophilic activation and infiltration (15), and eosinophil extravasation from the bone marrow into the lungs (4). Moreover, eosinophilia has been shown to be sustained by Th17 cells (26,27).…”

Section: Fig 1 Mechanisms Of Eosinophilic Immunopathology Linked Tomentioning

confidence: 99%

The potential role of Th17 immune responses in coronavirus immunopathology and vaccine-induced immune enhancement

Hotez

Bottazzi

Corry

2020

Microbes and Infection

107

115

View full text Add to dashboard Cite

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.

show abstract

Stop Press: Eosinophils Drafted to Join the Th17 Team

Abstract: Eosinophils are commonly associated with Th2 cell-driven inflammation. In this issue of Immunity, Griseri et al. (2015) identify a new GM-CSF-dependent role for eosinophils in the pathogenesis of IL-23-Th17 cell-induced colitis.

Cited by 18 publications

References 10 publications

Regulation of IL-12p40 by HIF controls Th1/Th17 responses to prevent mucosal inflammation

Regulation of IL-12p40 by HIF controls Th1/Th17 responses to prevent mucosal inflammation

COVID-19 vaccine design: the Janus face of immune enhancement

The potential role of Th17 immune responses in coronavirus immunopathology and vaccine-induced immune enhancement

Contact Info

Product

Resources

About