Adrian Liston

Research Summary

The Liston laboratory works on regulatory T cells. These are a type of white blood cell that act to suppress the rest of the immune response, preventing spontaneous autoimmune disease and acting as a rheostat to control just how active our immune system is. The number of these cells in our blood goes up as we get old, which may contribute to the immune-suppressed state of older persons. We seek to understand these cells, using both patient material and mouse models, so that we can harness their power to fine-tune the immune system for healthy ageing.
 

Latest Publications

Primary Sjögren's syndrome and high type I interferon signalling in a kindred with C2 deficiency.
Willemsen M, Van Nieuwenhove E, Seyed Tabib NS, Staels F, Schrijvers R, De Somer L, Liston A, Humblet-Baron S, Wouters C

n/a

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Rheumatology advances in practice, 6, 1, 2022

PMID: 35368972

Open Access

AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model.
Marino M, Zhou L, Rincon MY, Callaerts-Vegh Z, Verhaert J, Wahis J, Creemers E, Yshii L, Wierda K, Saito T, Marneffe C, Voytyuk I, Wouters Y, Dewilde M, Duqué SI, Vincke C, Levites Y, Golde TE, Saido TC, Muyldermans S, Liston A, De Strooper B, Holt MG

Single domain antibodies (VHHs) are potentially disruptive therapeutics, with important biological value for treatment of several diseases, including neurological disorders. However, VHHs have not been widely used in the central nervous system (CNS), largely because of their restricted blood-brain barrier (BBB) penetration. Here, we propose a gene transfer strategy based on BBB-crossing adeno-associated virus (AAV)-based vectors to deliver VHH directly into the CNS. As a proof-of-concept, we explored the potential of AAV-delivered VHH to inhibit BACE1, a well-characterized target in Alzheimer's disease. First, we generated a panel of VHHs targeting BACE1, one of which, VHH-B9, shows high selectivity for BACE1 and efficacy in lowering BACE1 activity in vitro. We further demonstrate that a single systemic dose of AAV-VHH-B9 produces positive long-term (12 months plus) effects on amyloid load, neuroinflammation, synaptic function, and cognitive performance, in the App Alzheimer's mouse model. These results constitute a novel therapeutic approach for neurodegenerative diseases, which is applicable to a range of CNS disease targets.

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EMBO molecular medicine, 14, 4, 07 Apr 2022

PMID: 35352880

Role for G-CSF in neutrophilic extramedullary myelopoiesis in a murine model of systemic juvenile idiopathic arthritis.
Malengier-Devlies B, Bernaerts E, Ahmadzadeh K, Filtjens J, Vandenhaute J, Boeckx B, Burton O, De Visscher A, Mitera T, Berghmans N, Verbeke G, Liston A, Lambrechts D, Proost P, Wouters C, Matthys P

Systemic juvenile idiopathic arthritis (sJIA) is a systemic inflammatory disease of childhood-onset. sJIA is associated with neutrophilia, including immature granulocytes, potentially driven by the growth factor granulocyte-colony stimulating factor (G-CSF). This study aimed to unravel the role of G-CSF in the pathology of sJIA.

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Arthritis & rheumatology (Hoboken, N.J.), 1, 1, 03 Mar 2022

PMID: 35243819