Life Sciences Research for Lifelong Health

Adrian Liston

Adrian is in the process of relocating to the Institute. You can find out more about his previous research on his lab website.

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-supressed 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

No Functional Role for microRNA-342 in a Mouse Model of Pancreatic Acinar Carcinoma.
Dooley J, Lagou V, Pasciuto E, Linterman MA, Prosser HM, Himmelreich U, Liston A

The intronic microRNA (miR)-342 has been proposed as a potent tumor-suppressor gene. miR-342 is found to be downregulated or epigenetically silenced in multiple different tumor sites, and this loss of expression permits the upregulation of several key oncogenic pathways. In several different cell lines, lower miR-342 expression results in enhanced proliferation and metastasis potential, both in vitro and in xenogenic transplant conditions. Here, we sought to determine the function of miR-342 in an in vivo spontaneous cancer model, using the Ela1-TAg transgenic model of pancreatic acinar carcinoma. Through longitudinal magnetic resonance imaging monitoring of Ela1-TAg transgenic mice, either wild-type or knockout for miR-342, we found no role for miR-342 in the development, growth rate, or pathogenicity of pancreatic acinar carcinoma. These results indicate the importance of assessing miR function in the complex physiology of in vivo model systems and indicate that further functional testing of miR-342 is required before concluding it is a bona fide tumor-suppressor-miR.

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Frontiers in oncology, 7, , 101, 2017

PMID: 28573106

Homeostasis-altering molecular processes as mechanisms of inflammasome activation.
Liston A, Masters SL

The innate immune system uses a distinct set of germline-encoded pattern recognition receptors (PRRs) to initiate downstream inflammatory cascades. This recognition system is in stark contrast to the adaptive immune system, which relies on highly variable, randomly generated antigen receptors. A key limitation of the innate immune system's reliance on fixed PRRs is its inflexibility in responding to rapidly evolving pathogens. Recent advances in our understanding of inflammasome activation suggest that the innate immune system also has sophisticated mechanisms for responding to pathogens for which there is no fixed PRR. This includes the recognition of debris from dying cells, known as danger-associated molecular patterns (DAMPs), which can directly activate PRRs in a similar manner to pathogen-associated molecular patterns (PAMPs). Distinct from this, emerging data for the inflammasome components NLRP3 (NOD-, LRR- and pyrin domain-containing 3) and pyrin suggest that they do not directly detect molecular patterns, but instead act as signal integrators that are capable of detecting perturbations in cytoplasmic homeostasis, for example, as initiated by infection. Monitoring these perturbations, which we term 'homeostasis-altering molecular processes' (HAMPs), provides potent flexibility in the capacity of the innate immune system to detect evolutionarily novel infections; however, HAMP sensing may also underlie the sterile inflammation that drives chronic inflammatory diseases.

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Nature reviews. Immunology, 17, 1474-1741, 208-214, 2017

PMID: 28163301

Defective germinal center B-cell response and reduced arthritic pathology in microRNA-29a-deficient mice.
van Nieuwenhuijze A, Dooley J, Humblet-Baron S, Sreenivasan J, Koenders M, Schlenner SM, Linterman M, Liston A

MicroRNA (miR) are short non-coding RNA sequences of 19-24 nucleotides that regulate gene expression by binding to mRNA target sequences. The miR-29 family of miR (miR-29a, b-1, b-2 and c) is a key player in T-cell differentiation and effector function, with deficiency causing thymic involution and a more inflammatory T-cell profile. However, the relative roles of different miR-29 family members in these processes have not been dissected. We studied the immunological role of the individual members of the miR-29 family using mice deficient for miR-29a/b-1 or miR-29b-2/c in homeostasis and during collagen-induced arthritis. We found a definitive hierarchy of immunological function, with the strong phenotype of miR-29a-deficiency in thymic involution and T-cell activation being reduced or absent in miR-29c-deficient mice. Strikingly, despite elevating the Th1 and Th17 responses, loss of miR-29a conferred near-complete protection from collagen-induced arthritis (CIA), with profound defects in B-cell proliferation and antibody production. Our results identify the hierarchical structure of the miR-29 family in T-cell biology, and identify miR-29a in B cells as a potential therapeutic target in arthritis.

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Cellular and molecular life sciences : CMLS, , 1420-9071, , 2017

PMID: 28124096

 

Group Members

Latest Publications

No Functional Role for microRNA-342 in a Mouse Model of Pancreatic Acinar Carcinoma.

Dooley J, Lagou V, Pasciuto E

Frontiers in oncology
7 :101 (2017)

PMID: 28573106

Homeostasis-altering molecular processes as mechanisms of inflammasome activation.

Liston A, Masters SL

Nature reviews. Immunology
17 1474-1741:208-214 (2017)

PMID: 28163301

Defective germinal center B-cell response and reduced arthritic pathology in microRNA-29a-deficient mice.

van Nieuwenhuijze A, Dooley J, Humblet-Baron S

Cellular and molecular life sciences : CMLS
1420-9071: (2017)

PMID: 28124096

Shaping Variation in the Human Immune System.

Liston A, Carr EJ, Linterman MA

Trends in immunology
1471-4981: (2016)

PMID: 27693120

Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation.

Masters SL, Lagou V, Jéru I

Science translational medicine
8 1946-6242:332ra45 (2016)

PMID: 27030597

Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes.

Dooley J, Tian L, Schonefeldt S

Nature genetics
48 1546-1718:519-27 (2016)

PMID: 26998692

The cellular composition of the human immune system is shaped by age and cohabitation.

Carr EJ, Dooley J, Garcia-Perez JE

Nature immunology
1529-2916: (2016)

PMID: 26878114

Premature thymic involution is independent of structural plasticity of the thymic stroma.

Franckaert D, Schlenner SM, Heirman N

European journal of immunology
1521-4141: (2015)

PMID: 25627671

Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3(+) and Foxp3(-) T cells.

Franckaert D, Dooley J, Roos E

Immunology and cell biology
1440-1711: (2014)

PMID: 25533288

Homeostatic control of regulatory T cell diversity.

Liston A, Gray DH

Nature reviews. Immunology
14 1474-1741:154-65 (2014)

PMID: 24481337

Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3⁺ regulatory T cells.

Pierson W, Cauwe B, Policheni A

Nature immunology
14 1529-2916:959-65 (2013)

PMID: 23852275

MicroRNA regulation of T-cell development.

Dooley J, Linterman MA, Liston A

Immunological reviews
253 1600-065X:53-64 (2013)

PMID: 23550638