Safeguarding lymphatic identity: cooperative Erg and Fli1 activity in lymphatic vascular homeostasis
Kelly de Korodi, Tatiana V. Petrova
Kelly de Korodi, Tatiana V. Petrova
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Commentary

Safeguarding lymphatic identity: cooperative Erg and Fli1 activity in lymphatic vascular homeostasis

Abstract

Although transcriptional programs driving lymphatic endothelial cell (LEC) specification are being increasingly characterized, far less is known about the postnatal mechanisms that preserve lymphatic vessel identity and function. In this issue of the JCI, Yang et al. show that the E26 transformation-specific (ETS) transcription factors ETS-related gene (Erg) and Friend leukemia integration 1 (Fli1) cooperatively maintain adult LEC homeostasis by sustaining transcriptionally distinct LEC populations, vascular integrity, immune-vascular interactions, and repression of proinflammatory and prothrombotic gene programs. These findings extend the known roles of Erg and Fli1 beyond the blood endothelium and provide mechanistic insight into human lymphatic disease associated with Erg haploinsufficiency.

Authors

Kelly de Korodi, Tatiana V. Petrova

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Figure 1

Cooperative action of Erg and Fli1 maintains lymphatic endothelial identity, specialization, and function.

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Cooperative action of Erg and Fli1 maintains lymphatic endothelial ident...
(A) Adult lymphatic vasculature consists of capillary lymphatic vessels, which take up interstitial fluid and serve as the entry point for DCs, and collecting vessels, which transport lymph to draining lymph nodes. Intraluminal valves ensure directional lymph flow. (B) In Yang et al. (22), loss of Erg and Fli1 resulted in the breakdown of the core lymphatic endothelial transcriptional program, including downregulation of Ccl21, encoding a key chemoattractant for DC migration. LECs also aberrantly acquired valve-like characteristics and activated proinflammatory and prothrombotic gene programs. Functionally, the combined loss of Erg and Fli1 disrupted essential lymphatic functions, leading to compromised lymph transport, impaired DC trafficking, and progressive degeneration of lymphatic valves.