Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

Palikuqi, Brisa; Rispal, Jérémie; Reyes, Efren; Vaka, Dedeepya; Boffelli, Dario; Klein, Ophir D.

doi:10.1016/j.stem.2022.07.007

Cited by 26 publications

(15 citation statements)

References 64 publications

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“…LECs are resistant to IR-related apoptosis and expand after IR exposure, where they serve as an essential source of pro-regenerative niche factors such as RSPO3, Wnt2a, and Ccl21a (Goto et al, 2022; Niec et al, 2022; Ogasawara et al, 2018; Palikuqi et al, 2022). Given this established role of lymphatics in intestinal regeneration, we sought to investigate if there could be crosstalk between LECs and Hdc + IMCs after injury.…”

Section: Resultsmentioning

confidence: 99%

“…Breaches of the intestinal barrier cause disruptions to the balance of normal microbial interactions, requiring a response from the host to restore homeostasis. LECs have been established as key niche cells for the ISC, as they expand during injury and are a major source of RSPO3 (Goto et al, 2022; Niec et al, 2022; Ogasawara et al, 2018; Palikuqi et al, 2022). While LECs have been shown to be central to the intestinal regeneration program, the mechanisms leading to their activation following injury were not known.…”

Section: Discussionmentioning

confidence: 99%

“…Pre-collector LECs surround the crypt base and associate with ISCs to regulate their activity (Niec et al, 2022). This LEC population expands in the intestine after whole-body irradiation (WB-IR), and conditional knockout of the Rspo3 gene in LECs hinders intestinal regeneration after WB-IR or 5FU chemotoxic injury, highlighting the importance of LEC-derived RSPO3 in this setting (Goto et al, 2022; Palikuqi et al, 2022). Lymphatics also expand in the bone after WB-IR and participate in regeneration (Biswas et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

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Immature myeloid cells are indispensable for intestinal regeneration post irradiation injury

Jiang

Waterbury

et al. 2023

Preprint

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SUMMARYThe intestinal epithelium functions both in nutrient absorption and as a barrier, separating the luminal contents from a network of vascular, fibroblastic, and immune cells underneath. Following injury to the intestine, multiple different cell populations cooperate to drive regeneration of the mucosa. Immature myeloid cells (IMCs), marked by histidine decarboxylase (Hdc), participate in regeneration of multiple organs such as the colon and central nervous system. Here, we found that IMCs infiltrate the injured intestine and promote epithelial regeneration and modulate LEC activity. IMCs produce prostaglandin E2 (PGE2), which promotes LEC lymphangiogenesis and upregulation of pro-regenerative factors including RSPO3. Moreover, we found that IMC recruitment into the intestine is driven by invading microbial signals. Accordingly, antibiotic eradication of the intestinal microbiome prior to WB-IR inhibits IMC recruitment, and consequently, intestinal recovery. We propose that IMCs play a critical role in intestinal repair and implicate gut microbes as mediators of intestinal regeneration.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immature myeloid cells are indispensable for intestinal regeneration post irradiation injury

Jiang

Waterbury

et al. 2023

Preprint

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“…Lymphatics are also involved in tumour metastasis [ 60 ] and inflammatory response regulation [ 61 ]. Besides, lymphatic endothelial cells have been reported to play an essential role in cardiac growth and repair [ 62 ] as well as in intestinal repair [ 63 ] via lymphangiocrine signalling.…”

Section: Lymphatic Systemmentioning

confidence: 99%

Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease

Uddin

Rutar

2022

IJMS

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Clearance of ocular fluid and metabolic waste is a critical function of the eye in health and disease. The eye has distinct fluid outflow pathways in both the anterior and posterior segments. Although the anterior outflow pathway is well characterized, little is known about posterior outflow routes. Recent studies suggest that lymphatic and glymphatic systems play an important role in the clearance of fluid and waste products from the posterior segment of the eye. The lymphatic system is a vascular network that runs parallel to the blood circulatory system. It plays an essential role in maintenance of fluid homeostasis and immune surveillance in the body. Recent studies have reported lymphatics in the cornea (under pathological conditions), ciliary body, choroid, and optic nerve meninges. The evidence of lymphatics in optic nerve meninges is, however, limited. An alternative lymphatic system termed the glymphatic system was recently discovered in the rodent eye and brain. This system is a glial cell-based perivascular network responsible for the clearance of interstitial fluid and metabolic waste. In this review, we will discuss our current knowledge of ocular lymphatic and glymphatic systems and their role in retinal degenerative diseases.

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“…Important in this process are actively cycling Lgr5+ intestinal stem cells (ISCs) at the crypt base, which are supported by epithelial, stromal, and immune cell niches [14][15][16][17] . These ISCs are maintained by niche-derived growth factors and developmental signalling pathways, such as WNT, NOTCH, BMP inhibitors, and EGF 18 , but are also regulated by environmental factors, such as the microbiome and diet 1,9,19,20 .…”

Section: Introductionmentioning

confidence: 99%

Post-fast refeeding enhances intestinal stem cell-mediated regeneration and tumourigenesis through mTORC1-dependent polyamine synthesis

Imada¹,

Shin²,

Khawaled³

et al. 2023

Preprint

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For more than a century, fasting regimens have improved health, lifespan, and tissue regeneration in diverse organisms, including humans. However, how fasting and post-fast refeeding impact adult stem cells and tumour formation has yet to be explored in depth. Here, we demonstrate that post-fast refeeding increases intestinal stem cell (ISC) proliferation and tumour formation: Post-fast refeeding augments the regenerative capacity of Lgr5+ intestinal stem cells (ISCs), and loss of the tumour suppressor Apc in ISCs under post-fast refeeding leads to a higher tumour incidence in the small intestine and colon than in the fasted or ad libitum (AL) fed states. This demonstrates that post-fast refeeding is a distinct state. Mechanistically, we discovered that robust induction of mTORC1 in post-fast-refed ISCs increases protein synthesis via polyamine metabolism to drive these changes, as inhibition of mTORC1, polyamine metabolite production, or protein synthesis abrogates the regenerative or tumourigenic effects of post-fast refeeding. Thus, fast-refeeding cycles must be carefully considered when planning diet-based strategies for regeneration without increasing cancer risk, as post-fast refeeding leads to a burst not only in stem cell-driven regeneration but also in tumourigenicity.

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Lymphangiocrine signals are required for proper intestinal repair after cytotoxic injury

Cited by 26 publications

References 64 publications

Immature myeloid cells are indispensable for intestinal regeneration post irradiation injury

Immature myeloid cells are indispensable for intestinal regeneration post irradiation injury

Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease

Post-fast refeeding enhances intestinal stem cell-mediated regeneration and tumourigenesis through mTORC1-dependent polyamine synthesis

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