ST2 receptor invalidation maintains wound inflammation, delays healing and increases fibrosis

Lee, James S.; Seppanen, Elke; Patel, Jatin; Rodero, Mathieu P; Khosrotehrani, Kiarash

doi:10.1111/exd.12833

Cited by 23 publications

(23 citation statements)

References 13 publications

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“…39,40 This macrophage population represents the first line of defense against microbes breaching the intestine and ascendant gynecological infections. 22 As has been reported for other sites, 41-43 we observed that the peritoneal administration of IL-33 was able to promote an allergic like macrophage activation in the peritoneal tumor-associated macrophages. As reported previously for CD40 activated CD86 + activated macrophages in the microenvironment of pancreatic cancer, 44 or activated peritoneal macrophages were able to promote tumor cytotoxicity in vitro and delay tumor progression in vivo.…”

Section: Discusionsupporting

confidence: 77%

IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment

et al. 2018

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Ovarian cancer is frequently diagnosed as peritoneal carcinomatosis. Unlike other tumor locations, the peritoneal cavity is commonly exposed to gut-breaching and ascending genital microorganisms and has a unique immune environment. IL-33 is a local cytokine that can activate innate and adaptive immunity. We studied the effectiveness of local IL-33 delivery in the treatment of cancer that has metastasized to the peritoneal cavity. Direct peritoneal administration of IL-33 delayed the progression of metastatic peritoneal cancer. Prolongation in survival was not associated with a direct effect of IL-33 on tumor cells, but with major changes in the immune microenvironment of the tumor. IL-33 promoted a significant increase in the leukocyte compartment of the tumor immunoenvironment and an allergic cytokine profile. We observed a substantial increase in the number of activated CD4+ T-cells accompanied by peritoneal eosinophil infiltration, B-cell activation and activation of peritoneal macrophages which displayed tumoricidal capacity. Depletion of CD4+ cells, eosinophils or macrophages reduced the anti-tumor effects of IL-33 but none of these alone were sufficient to completely abrogate its positive benefit. In conclusion, local administration of IL-33 generates an allergic tumor environment resulting in a novel approach for treatment of metastatic peritoneal malignancies, such as advanced ovarian cancer.

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Section: Discusionsupporting

confidence: 77%

IL-33 delays metastatic peritoneal cancer progression inducing an allergic microenvironment

et al. 2018

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“…The roles for cholesterol in peripheral tissues have been previously described. In the skin, cholesterol is a protagonist in the development of the epidermal permeability barrier, is a precursor for the synthesis of local steroid hormones, and influences keratinocyte differentiation, corneocyte desquamation, barrier repair and melanogenesis . Yet there remains one important skin appendage in which the role of cholesterol is yet to be fully explored, namely the hair follicle (HF).…”

Section: Introductionmentioning

confidence: 99%

Cholesterol homeostasis: Links to hair follicle biology and hair disorders

Palmer

Blakeborough

Harries

et al. 2019

Experimental Dermatology

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Lipids and lipid metabolism are critical factors in hair follicle (HF) biology, and cholesterol has long been suspected of influencing hair growth. Altered cholesterol homeostasis is involved in the pathogenesis of primary cicatricial alopecia, mutations in a cholesterol transporter are associated with congenital hypertrichosis, and dyslipidaemia has been linked to androgenic alopecia. The underlying molecular mechanisms by which cholesterol influences pathways involved in proliferation and differentiation within HF cell populations remain largely unknown. As such, expanding our knowledge of the role for cholesterol in regulating these processes is likely to provide new leads in the development of treatments for disorders of hair growth and cycling. This review describes the current state of knowledge with respect to cholesterol homeostasis in the HF along with known and putative links to hair pathologies.

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“…The authors focused on inflammatory aspects of the phenotype, which will have clear parallels to skin disease. Using FACS analysis of digested 4 day wound tissue, Lee et al revealed unaltered overall numbers of macrophages, but a shift in the cell phenotype with ST2 wounds containing many more Ly6c + ; MHCII − cells which the authors suggest indicates impaired switching from the M1 (classically activated) to M2 (alternatively activated) macrophage state . It would have been nice to see this confirmed with additional macrophage polarization markers and over a full wound healing time course, to fully understand the phenotype and kinetics of wound macrophage recruitment/retention.…”

mentioning

confidence: 99%

“…Given its widely documented role in skin and inflammatory disease, it is somewhat surprising that IL33‐ST2 signalling has been apparently overlooked in the skin wound repair literature. In this issue of Experimental Dermatology, Lee et al correct this oversight by reporting the effects of genetic ST2 ablation on murine wound repair . At first glance, there appeared no difference between ST2 null and wild‐type mice in excisional wound closure (measured via digital planimetry), a comparatively insensitive analysis method .…”

mentioning

confidence: 99%

“…At first glance, there appeared no difference between ST2 null and wild‐type mice in excisional wound closure (measured via digital planimetry), a comparatively insensitive analysis method . Thankfully, Lee et al continued to histological analysis of healing where they report delayed re‐epithelialization, reduced angiogenesis and a more immature composition of collagen present within the wound granulation tissue .…”

mentioning

confidence: 99%

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