International Partnering Award with the USA to investigate signalling pathways that regulate human immunity during ageing
Lead Research Organisation:
University College London
Department Name: Immunology and Molecular Pathology
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
People |
ORCID iD |
| Arne Akbar (Principal Investigator) |
Publications
Akbar AN
(2016)
Senescence of T Lymphocytes: Implications for Enhancing Human Immunity.
in Trends in immunology
Byng-Maddick R
(2017)
Tumor Necrosis Factor (TNF) Bioactivity at the Site of an Acute Cell-Mediated Immune Response Is Preserved in Rheumatoid Arthritis Patients Responding to Anti-TNF Therapy.
in Frontiers in immunology
Covre L
(2019)
Circulating Senescent T Cells Are Linked to Systemic Inflammation and Lesion Size During Human Cutaneous Leishmaniasis
in Frontiers in Immunology
Haas CT
(2016)
Diagnostic 'omics' for active tuberculosis.
in BMC medicine
Henson SM
(2015)
Blockade of PD-1 or p38 MAP kinase signaling enhances senescent human CD8(+) T-cell proliferation by distinct pathways.
in European journal of immunology
Pereira BI
(2016)
Convergence of Innate and Adaptive Immunity during Human Aging.
in Frontiers in immunology
Pollara G
(2017)
Validation of Immune Cell Modules in Multicellular Transcriptomic Data.
in PloS one
Rivino L
(2015)
Virus-specific T lymphocytes home to the skin during natural dengue infection
in Science Translational Medicine
Seidel JA
(2018)
Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function.
in Clinical and experimental immunology
Shih BB
(2017)
Derivation of marker gene signatures from human skin and their use in the interpretation of the transcriptional changes associated with dermatological disorders.
in The Journal of pathology
| Description | We have investigated immune cells in the skin of older humans. These subjects have decreased ability to respond to respond to microorganisms that they were immune to when they were younger. We found that the immune cells in the skin were fully functional, however they were inhibited from acting by other cells in the skin. In addition, we found that inflammatory environment in the old skin precludes efficient immune response to challenge with viral antigen. If this inflammation is blocked over a short period of time, immune reponses in older individuals is improved. Part of this grant involves joint studies with the Drs. Bonnie Blomberg and Daniela Frasca at the University of Miami on the ageing of B cells. This collaboration has led to the application of a Welcome Trust Senior Investigator award with Akbar as the PI and Blomberg and Frasca as collaborators. |
| Exploitation Route | Our studies suggest that when trying to boost the immune system during ageing, it would be beneficial to remove the inhibitory influences that are present in the skin , rather then to boost the activity of the immune cells. Short term blocking of inflammation with a p38MAPK inhibitor provided by GSK led to improved response to antigen-specific challenge in the skin. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Collaboration with the Rockefeller University, to generate and analyse microarray data of normal and antigen challenged human skin from young and old individuals to investigate the mechanisms for age related changes in cutaneous immunity. |
| Organisation | Rockefeller University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | This collaboration provided the expertise and the facilities to generate a unique resource: transcriptional data sets of normal and antigen challenged human skin from young and old individuals to investigate the mechanisms for age related changes in cutaneous immunity. This is a unique resource which allows us (and others) to examine age related changes at a transcriptional level in normal skin and skin challenged with recall antigen. |
| Collaborator Contribution | This collaboration provided the expertise and the facilities to generate a unique resource: transcriptional data sets of normal and antigen challenged human skin from young and old individuals to investigate the mechanisms for age related changes in cutaneous immunity. This is a unique resource which allows us (and others) to examine age related changes at a transcriptional level in normal skin and skin challenged with recall antigen. |
| Impact | doi: 10.1038/jid.2015.63. |
| Start Year | 2012 |
| Description | Daniela Frasca / Bonnie B. Blomberg |
| Organisation | University of Miami |
| Department | Miller School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Exchange of research ideas and techniques including manipulation of senescence associated signalling pathways |
| Collaborator Contribution | Exchange of research ideas and techniques including manipulation of senescence associated signalling pathways |
| Impact | Exchange of techniques |
| Start Year | 2015 |
| Description | SILKE PAUST |
| Organisation | Baylor College of Medicine |
| Department | Department of Pediatrics |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Provision of paired human PBMC and skin derived immune cells following antigen challenge and skin blister. |
| Collaborator Contribution | Analysis of NK cell immune responses in skin and blood. |
| Impact | Generation of data that will be included in an original research article. |
| Start Year | 2014 |