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Comment
. 2023 Sep;44(9):558-560.
doi: 10.1016/j.tips.2023.05.005. Epub 2023 Jun 7.

Hedgehog signalling in allograft vasculopathy: a new therapeutic target?

Jasmine Rowell  1 , Ching-In Lau  1 , Diana C Yánez  1 , Eden Zhang  1 , Tessa Crompton  2
Affiliations
Comment

Hedgehog signalling in allograft vasculopathy: a new therapeutic target?

Jasmine Rowell et al. Trends Pharmacol Sci. 2023 Sep.

Abstract

Allograft vasculopathy (AV) leads to chronic rejection of organ transplants, but its causes are obscure. New research from the Jane-Wit laboratory showed that Sonic Hedgehog (SHH) signalling from damaged graft endothelium drives vasculopathy by promoting proinflammatory cytokine production and NLRP3-inflammasome activation in alloreactive CD4+PTCH1hiPD-1hiT memory cells, offering new diagnostic and therapeutic strategies.

Keywords: CD4 T cell; NLRP3; SMO; Sonic Hedgehog (SHH); ZFYVE21; inflammasome.

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Conflict of interest statement

Declaration of interests The authors declare no financial or commercial conflicts of interest.

Figures

Figure 1.
Figure 1.. Mechanism of allograft vasculopathy (AV).
The cartoon illustrates the newly described mechanism of AV [1]. Ischaemia–reperfusion injury (IRI) leads to Sonic Hedgehog (SHH) secretion by endothelial cells which promotes type I interferon γ (IFN-γ) responses in alloreactive CD4+PTCH1hiPD1hiTmem cells. SHH activates Smoothened (SMO) signalling which leads to induction of zinc finger protein ZFYVE21. ZFYVE21 activates NLRP3 inflammasomes causing enhanced IFN-γ expression and interleukin 18 (IL-18) secretion, further driving the alloreactive response and leading to AV. The cartoon highlights novel possible therapeutic or diagnostic strategies for AV (numbered). Abbreviations: DHH, Desert Hedgehog; IHH, Indian Hedgehog; PD1, programmed death 1 protein; PTCH1, Patched1; TCR, T cell receptor. Figure created with BioRender.
See this image and copyright information in PMC

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References

    1. Lee RT et al. (2016) Hedgehog signalling. Development 143, 367–372 - PubMed
    1. Lau CI et al. (2022) Sonic Hedgehog signalling in the regulation of barrier tissue homeostasis and inflammation. FEBS J 289, 8050–8061 - PubMed
    1. Pober JS et al. (2021) Cardiac allograft vasculopathy: current review and future research directions. Cardiovasc. Res 117, 2624–2638 - PMC - PubMed
    1. Merola J et al. (2017) Recent advances in allograft vasculopathy. Curr. Opin. Organ Transplant 22, 1–7 - PMC - PubMed
    1. Jiang B et al. (2023) Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells. Sci. Signal 16, eabo3406. - PMC - PubMed

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