Cutaneous Immunology
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
We are working towards treatment and prevention of immune-mediated skin disease. The skin is often the first point of contact with pathogens and allergens, but relatively little is understood about how the cutaneous immune system clears these challenges. Such knowledge is vitally important to understanding the mechanisms of skin disease and related diseases, and for developing more effective ways of cutaneous drug and vaccine delivery. It is increasingly clear that skin barrier dysfunction is an important first step in the development of atopic eczema, one of the commonest skin diseases in the UK, and often associated with asthma and rhinitis. The barrier dysfunction promotes entry of allergens and microbes which eventually lead to skin inflammation. The latter is treated with topical immune suppressants, but these are not curative and also carry risks of side effects. We wish to understand the steps linking barrier dysfunction and skin inflammation, as these will provide opportunities for new treatments. In particular, we will explore ways to repair barrier function and to understand the roles of novel immune cells in contributing to the inflammation. These findings will have implications for atopic eczema, but also for other forms of inflammatory skin disease and indeed for the improvement of vaccine delivery in to the skin.
Technical Summary
Atopic disease affects 20-30% of the UK population and includes atopic eczema, asthma and rhinitis. Current treatments are suppressive, but not curative, and carry risks of side-effects. Since the identification of an association between atopic eczema and null mutations in the gene encoding filaggrin, it has become increasingly clear that events in the epithelium represent critical susceptibility factors in disease pathogenesis. We are working towards an understanding of the pathogenesis of atopic disease, in particular to explain how the epidermal dysfunction associated with filaggrin insufficiency contributes to atopic disease and whether this can be modified therapeutically. We capitalize on the ready access to lesional tissue in humans, and to function within networks and collaborations to maximize opportunities for success. The aim of the research is to understand the pathogenesis of cutaneous atopic disease in order to inform new approaches to disease prevention and treatment. The studies will also contribute to our understanding of the interaction between the epithelium and the innate and adaptive immune response. Emphasis will be focused on: 1) how filaggrin insufficiency promotes atopic inflammation and whether this can be therapeutically modified; 2) characterising innate IL-13 producing cells in human lesional atopic skin and after antigen challenge; 3) understanding mechanisms underlying antigen-specific immunotherapy to modulate immune responses in humans and to translate these findings to patient benefit; 4) investigating mechanisms underlying the cellular immune response to viral antigens in human skin. The experimental design is based on isolation of cells from blood and skin of patients and controls. The cells from skin include keratinocytes, dendritic cell family members (eg Langerhans cells), T cells, innate lymphoid cells. The patients will include those with cutaneous atopic disease and other inflammatory skin diseases, as well as individuals before and after cutaneous antigen challenge. Studies will be undertaken ex vivo and after culture. Interactions between keratinocytes, Langerhans cells and immune effector cells will include examination by expression analyses, mediator production and functional keratinocyte outcomes such as barrier function. Molecular mechanisms underlying these findings will be investigated. As well as contributing to disease and tissue specific questions, these studies will advance the broader University Unit aims of defining the interactions between the innate and adaptive immune responses and the local micro-environment, which in turn will support the development of new approaches to vaccination and treatment.
Organisations
- University of Oxford (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- University of Sri Jayawardanapura (Collaboration)
- HARVARD UNIVERSITY (Collaboration)
- Newcastle University (Collaboration)
- UNIVERSITY OF BIRMINGHAM (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- Monash University (Collaboration)
People |
ORCID iD |
Graham Ogg (Principal Investigator) |
Publications
Agache I
(2021)
EAACI Biologicals Guidelines-dupilumab for children and adults with moderate-to-severe atopic dermatitis.
in Allergy
Bosma AL
(2023)
Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types.
in JAAD international
Buckley PR
(2022)
HLA-dependent variation in SARS-CoV-2 CD8 + T cell cross-reactivity with human coronaviruses.
in Immunology
Chen Y
(2020)
Innate Lymphocyte Mechanisms in Skin Diseases
in Annual Review of Immunology
Chen Y
(2023)
Group A Streptococcus induces CD1a-autoreactive T cells and promotes psoriatic inflammation
in Science Immunology
Chen YL
(2020)
Re-evaluation of human BDCA-2+ DC during acute sterile skin inflammation.
in The Journal of experimental medicine
Chen YL
(2019)
Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis.
in Science translational medicine
Cork MJ
(2020)
Atopic dermatitis epidemiology and unmet need in the United Kingdom.
in The Journal of dermatological treatment
Cotton R
(2021)
Human skin is colonized by T cells that recognize CD1a independently of lipid
in Journal of Clinical Investigation
Cotton R
(2021)
CD1a selectively captures endogenous cellular lipids that broadly block T cell response
in Journal of Experimental Medicine
COvid-19 Multi-Omics Blood ATlas (COMBAT) Consortium. Electronic Address: Julian.knight@well.ox.ac.uk
(2022)
A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.
in Cell
Cross AR
(2023)
Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury.
in JCI insight
Dayarathna S
(2020)
Similarities and differences between the 'cytokine storms' in acute dengue and COVID-19
in Scientific Reports
De Jong A
(2021)
CD1a function in human skin disease.
in Molecular immunology
De Silva T
(2021)
The Impact of Viral Mutations on Recognition by SARS-CoV-2 Specific T-Cells
in SSRN Electronic Journal
Fonseka CL
(2022)
Dengue virus co-opts innate type 2 pathways to escape early control of viral replication.
in Communications biology
Gomes L
(2022)
Surveillance of SARS-CoV-2 variants of concern by identification of single nucleotide polymorphisms in the spike protein by a multiplex real-time PCR.
in Journal of virological methods
Gutowska-Owsiak D
(2020)
Addressing Differentiation in Live Human Keratinocytes by Assessment of Membrane Packing Order.
in Frontiers in cell and developmental biology
Gutowska-Owsiak D
(2018)
Orchestrated control of filaggrin-actin scaffolds underpins cornification.
in Cell death & disease
Hardman C
(2019)
Fevipiprant, a selective prostaglandin D2 receptor 2 antagonist, inhibits human group 2 innate lymphoid cell aggregation and function.
in The Journal of allergy and clinical immunology
Hardman C
(2021)
IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent
in Science Immunology
Hardman CS
(2022)
CD1a promotes systemic manifestations of skin inflammation.
in Nature communications
Hilvering B
(2018)
Synergistic activation of pro-inflammatory type-2 CD8+ T lymphocytes by lipid mediators in severe eosinophilic asthma.
in Mucosal immunology
Huang S
(2023)
CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms
in Cell
Hudson D
(2023)
Can we predict T cell specificity with digital biology and machine learning?
in Nature reviews. Immunology
Jayathilaka D
(2018)
Role of NS1 antibodies in the pathogenesis of acute secondary dengue infection.
in Nature communications
Jayathilaka D
(2022)
Kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222.
in Clinical and experimental immunology
Jeewandara C
(2022)
Sensitivity and specificity of two WHO approved SARS-CoV2 antigen assays in detecting patients with SARS-CoV2 infection
in BMC Infectious Diseases
Jeewandara C
(2022)
Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac).
in Scientific reports
Jeewandara C
(2021)
Genomic and epidemiological analysis of SARS-CoV-2 viruses in Sri Lanka
Jeewandara C
(2022)
Kinetics of immune responses to the AZD1222/Covishield vaccine with varying dose intervals in Sri Lankan individuals.
in Immunity, inflammation and disease
Jeewandara C
(2022)
Immune responses to Sinopharm/BBIBP-CorV in individuals in Sri Lanka.
in Immunology
Jeewandara C
(2021)
Immune responses to a single dose of the AZD1222/Covishield vaccine in health care workers.
in Nature communications
Jeewandara C
(2018)
Cultured ELISpot Assay to Investigate Dengue Virus Specific T-Cell Responses.
in Methods in molecular biology (Clifton, N.J.)
Jeewandara C
(2022)
Comparison of the immunogenicity of five COVID-19 vaccines in Sri Lanka.
in Immunology
Jeewandara C
(2022)
Persistence of immune responses to the Sinopharm/BBIBP-CorV vaccine.
in Immunity, inflammation and disease
Jeewandara C
(2021)
SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute COVID-19 illness.
in Scientific reports
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_00008/1 | 31/03/2017 | 30/03/2023 | £2,738,000 | ||
MC_UU_00008/2 | Transfer | MC_UU_00008/1 | 31/03/2017 | 30/03/2023 | £1,821,000 |
MC_UU_00008/3 | Transfer | MC_UU_00008/2 | 31/03/2017 | 30/03/2023 | £2,257,000 |
MC_UU_00008/4 | Transfer | MC_UU_00008/3 | 31/03/2017 | 30/03/2023 | £1,459,000 |
MC_UU_00008/5 | Transfer | MC_UU_00008/4 | 31/03/2017 | 30/03/2023 | £1,346,000 |
MC_UU_00008/6 | Transfer | MC_UU_00008/5 | 31/03/2017 | 30/03/2023 | £1,660,000 |
MC_UU_00008/7 | Transfer | MC_UU_00008/6 | 31/03/2017 | 30/03/2023 | £401,000 |
MC_UU_00008/8 | Transfer | MC_UU_00008/7 | 31/03/2017 | 31/03/2024 | £2,876,000 |
MC_UU_00008/9 | Transfer | MC_UU_00008/8 | 31/03/2017 | 30/03/2023 | £2,568,000 |
MC_UU_00008/10 | Transfer | MC_UU_00008/9 | 31/03/2017 | 30/03/2023 | £2,060,000 |
MC_UU_00008/11 | Transfer | MC_UU_00008/10 | 31/03/2017 | 30/03/2023 | £1,477,000 |
Description | Multiple Clinical Guidelines Committee |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Impact | Multiple published clinical guidelines for broad impact globally |
Description | Anaptysbio Research Grant |
Amount | £700,000 (GBP) |
Organisation | AnaptysBio |
Sector | Private |
Country | United States |
Start | 02/2017 |
End | 01/2019 |
Description | CRN Translational dermatology |
Amount | £150,000 (GBP) |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 03/2023 |
End | 03/2024 |
Description | Celgene Fellowship |
Amount | £500,000 (GBP) |
Organisation | Bristol-Myers Squibb |
Department | Celgene |
Sector | Private |
Country | United States |
Start | 01/2016 |
End | 01/2020 |
Description | Comprehensive Research Network |
Amount | £1,700,000 (GBP) |
Organisation | National Institute for Health Research |
Department | NIHR Clinical Research Network (CRN) |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2007 |
End | 03/2017 |
Description | EXPLORATORY/DEVELOPMENT GRANT |
Amount | $137,000 (USD) |
Funding ID | 1R21AI125886-01 |
Organisation | National Institutes of Health (NIH) |
Sector | Public |
Country | United States |
Start | 08/2016 |
End | 08/2018 |
Description | Janssen Cartography |
Amount | £5,000,000 (GBP) |
Organisation | Janssen Research & Development |
Sector | Private |
Country | Global |
Start | 12/2021 |
End | 12/2024 |
Description | MRC/UCB Antibody Discovery Initiative |
Amount | £250,000 (GBP) |
Funding ID | MC_EX_MR/R022550/1 |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 02/2019 |
End | 12/2019 |
Description | NIHR Senioe Investigator |
Amount | £60,000 (GBP) |
Organisation | University of Leicester |
Department | NIHR Biomedical Research Centre |
Sector | Hospitals |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2022 |
Description | Oxford NIHR Biomedical Research Centre |
Amount | £400,000 (GBP) |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 09/2022 |
End | 03/2027 |
Description | Professor Graham Ogg |
Amount | £80,000 (GBP) |
Funding ID | NIHR203691 |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 03/2022 |
End | 03/2026 |
Description | Translational Skin Immunology |
Amount | £25,000,000 (GBP) |
Funding ID | UU_00036/2 |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2023 |
End | 03/2028 |
Description | UCB Research grant |
Amount | £354,000 (GBP) |
Organisation | UCB Pharma |
Sector | Private |
Country | United Kingdom |
Start | 08/2016 |
End | 08/2018 |
Description | Wellcome Trust Collaboratiev Award |
Amount | £3,000,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2018 |
End | 04/2023 |
Description | Andrew McKenzie LMB Cambridge |
Organisation | Medical Research Council (MRC) |
Department | MRC Laboratory of Molecular Biology (LMB) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are working with Andrew McKenzie to identify nuocytes in human and model skin and relate to clinical disease. we provide knowhow and expertise for access to human skin cells. |
Collaborator Contribution | Andrew McKenzie provides knowhow and expertise for access to model skin |
Impact | new collaboration |
Start Year | 2011 |
Description | Biomedical Research centre Oxford |
Organisation | University of Oxford |
Department | Nuffield Department of Clinical Medicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provided many of the samples and technology for analysis of samples using Biomedical Research Centre equipment. |
Collaborator Contribution | Access to equipment and individuals |
Impact | Many outputs as detailed in relevant sections |
Start Year | 2007 |
Description | Branch Moody Harvard |
Organisation | Harvard University |
Department | Harvard Medical School |
Country | United States |
Sector | Academic/University |
PI Contribution | We collaborate on CD1a-restricted T cell responses. We have contributed ideas, samples, experimental work and technical advances. |
Collaborator Contribution | We collaborate on CD1a-restricted T cell responses. Branch Moody and his team have contributed ideas, samples, experimental work and technical advances. |
Impact | Multiple publications and conference presentations |
Start Year | 2012 |
Description | Del Besra |
Organisation | University of Birmingham |
Department | Birmingham Clinical Trials Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Part of Wellcome Trust Collaborative Award |
Collaborator Contribution | lipid chemistry |
Impact | Not yet |
Start Year | 2018 |
Description | Jamie Rossjohn |
Organisation | Monash University |
Department | Monash Centre for Astrophysics |
Country | Australia |
Sector | Academic/University |
PI Contribution | Part of our Wellcome Trust Collaborative Award |
Collaborator Contribution | Biophysical and structural knowledge |
Impact | Not yet |
Start Year | 2018 |
Description | Muzlifah Haniffa |
Organisation | Newcastle University |
Department | Newcastle 85+ Study |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Part of Wellcome Trust Collaborative Award |
Collaborator Contribution | Dendritic cell biology |
Impact | Not yet |
Start Year | 2018 |
Description | Paul Klenerman VZV |
Organisation | Medical Research Council (MRC) |
Department | MRC Molecular Haematology Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Analysis of varicella zoster virus specific immune respoonses after vaccination |
Collaborator Contribution | Access to samples and discussions. |
Impact | Publications and presentations |
Start Year | 2008 |
Description | University of Sri Jayawardanapura |
Organisation | University of Sri Jayawardanapura |
Country | Sri Lanka |
Sector | Academic/University |
PI Contribution | Analyses of samples |
Collaborator Contribution | Contribution of samples and some analyses |
Impact | see relevant sections |
Start Year | 2008 |
Title | ANTIBODIES |
Description | The invention relates to an antibody or antigen binding fragment thereof which is capable of binding to CD1a, which is particularly suitable for treating or preventing one or more inflammatory skin or mucosal disorder, or disease or one or more associated systemic disease or disorder, or one or more inflammatory drug reaction which manifests systemically, or a CD1a-expressing malignancy |
IP Reference | WO2022248839 |
Protection | Patent / Patent application |
Year Protection Granted | 2022 |
Licensed | Commercial In Confidence |
Impact | Discussions underway |
Title | MODULATORS OF CD1 PROTEIN BINDING TO T CELL RECEPTORS |
Description | Identification of candidate modulator molecules for CD1 |
IP Reference | 63/411,971 |
Protection | Patent / Patent application |
Year Protection Granted | 2023 |
Licensed | No |
Impact | Commercial discussions underway |
Title | Phase 2 study of rupatadine efficacy in dengue infection |
Description | Phase 2 study of rupatadine efficacy in acute severe dengue infection |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2022 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
UKCRN/ISCTN Identifier | SLCTR/2017/024 |
Impact | Trend towards improved outcomes. suggests combination therapy may be worth investigating |
Title | Preliminary study on use of rupatadine |
Description | A preliminary study of the efficacy of rupatadine for the treatment of acute dengue infection |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2018 |
Development Status | Under active development/distribution |
Impact | To investigate use of a new, inexpensive treatment option |
Title | Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis |
Description | I run numerous clinical trials in Oxford to translate our research findings into clinical practice. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2019 |
Development Status | Under active development/distribution |
Impact | Contributed towards proividing a new treatment modality |
Title | TREAT - The Treatment of severe atopic eczema trial |
Description | A randomized controlled clinical trial protocol assessing the effectiveness, safety and cost-effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2018 |
Development Status | Under active development/distribution |
Impact | I run numerous cllinical trials in Oxford to translate our research findings into clinical practice |
Company Name | T-Cypher Bio |
Description | T-Cypher Bio develops TCR (T-Cell Receptor) discovery software designed to identify TCRs for the treatment of tumours and other diseases. |
Year Established | 2020 |
Impact | successful fund raising, and recruitment of executive team and staff |
Website | https://tcypherbio.com/ |
Description | "Cut & Paste" - genome editing (Royal Institution Family Fun day) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | "Cut & Paste" - genome editing activities at the Royal Institution Family Fun day on 22nd February 2019. It comprised three activities explaining genome editing and its utilisation as a research tool |
Year(s) Of Engagement Activity | 2019 |
Description | "Understanding allergy - Itching, sneezing, wheezing" |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Two 30 minute talks to 9/10 year students explaining the immune system and allergy. The talks were part of Wadham College Aspiration day 4th March 2019 - Academic taster session. |
Year(s) Of Engagement Activity | 2019 |
Description | CRN Podcast |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Podcast highlighting medical problems in dermatology and our strategies for developign new approaches to treatment. |
Year(s) Of Engagement Activity | 2019 |
Description | Newsletter 2023 |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Research activity newsletter |
Year(s) Of Engagement Activity | 2023 |
Description | Patient public talks and meeting 2023 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Presentations and talks to public and patients |
Year(s) Of Engagement Activity | 2023 |
Description | Science club at Freeland Primary School |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Visit to Freeland Primary School on 14th January 2020 to carry out a 1h session comprising three activities with primary school students to explain DNA and genome editing. |
Year(s) Of Engagement Activity | 2020 |
Description | T cell differentation |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | 1h session during Biology Summer School which took place at Wadham College on 21st August 2019. The activity looked at how naïve T cells differentiate into T cell subsets in vitro. |
Year(s) Of Engagement Activity | 2019 |
Description | The Immune Cell Highway |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other audiences |
Results and Impact | The Immune Cell Highway was a session organised for Superdads Playgroup at Northway Church, Oxford on 8th February 2020. The activities were aimed at explaining how immune cells move around the body via two pathways - the blood & the lymphatics - and how this travelling is essential for clearing infections in the skin. |
Year(s) Of Engagement Activity | 2020 |
Description | The Immune Cell Highway (Swindon Science Festival) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | The Immune Cell Highway activity links the work being done in the Dong, Ogg and Jackson labs in the WIMM. They have created a stand explaining how immune cells move around the body via two pathways: the blood & the lymphatics. This activity was part of Swindon Science Festival on 21st and 22nd February 2020. |
Year(s) Of Engagement Activity | 2020 |
Description | Understanding allergy - Itching, sneezing, wheezing |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Two 30 minute sessions doing an "allergy testing" experiment with 9/10 year students. These sessions were part of Wadham College Aspiration Day - Academic taster session on 10th May 2019. |
Year(s) Of Engagement Activity | 2019 |