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Article: The Influence of Cross-Reactive T Cells in COVID-19.

Eggenhuizen, Peter J / Ooi, Joshua D

2024 Volume 12, Issue 3

Abstract: Memory T cells form from the adaptive immune response to historic infections or vaccinations. Some memory T cells have the potential to recognise unrelated pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and generate cross- ... ...

Abstract	Memory T cells form from the adaptive immune response to historic infections or vaccinations. Some memory T cells have the potential to recognise unrelated pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and generate cross-reactive immune responses. Notably, such T cell cross-reactivity has been observed between SARS-CoV-2 and other human coronaviruses. T cell cross-reactivity has also been observed between SARS-CoV-2 variants from unrelated microbes and unrelated vaccinations against influenza A, tuberculosis and measles, mumps and rubella. Extensive research and debate is underway to understand the mechanism and role of T cell cross-reactivity and how it relates to Coronavirus disease 2019 (COVID-19) outcomes. Here, we review the evidence for the ability of pre-existing memory T cells to cross-react with SARS-CoV-2. We discuss the latest findings on the impact of T cell cross-reactivity and the extent to which it can cross-protect from COVID-19.
Language	English
Publishing date	2024-03-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12030564
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The interplay between the microbiota, diet and T regulatory cells in the preservation of the gut barrier in inflammatory bowel disease.

Prame Kumar, Kathryn / Ooi, Joshua D / Goldberg, Rimma

Frontiers in microbiology

2023 Volume 14, Page(s) 1291724

Abstract: Inflammatory bowel disease (IBD) is becoming more common in the Western world due to changes in diet-related microbial dysbiosis, genetics and lifestyle. Incidences of gut permeability can predate IBD and continued gut barrier disruptions increase the ... ...

Abstract	Inflammatory bowel disease (IBD) is becoming more common in the Western world due to changes in diet-related microbial dysbiosis, genetics and lifestyle. Incidences of gut permeability can predate IBD and continued gut barrier disruptions increase the exposure of bacterial antigens to the immune system thereby perpetuating chronic inflammation. Currently, most of the approved IBD therapies target individual pro-inflammatory cytokines and pathways. However, they fail in approximately 50% of patients due to their inability to overcome the redundant pro inflammatory immune responses. There is increasing interest in the therapeutic potential of T regulatory cells (Tregs) in inflammatory conditions due to their widespread capability to dampen inflammation, promote tolerance of intestinal bacteria, facilitate healing of the mucosal barrier and ability to be engineered for more targeted therapy. Intestinal Treg populations are inherently shaped by dietary molecules and gut microbiota-derived metabolites. Thus, understanding how these molecules influence Treg-mediated preservation of the intestinal barrier will provide insights into immune tolerance-mediated mucosal homeostasis. This review comprehensively explores the interplay between diet, gut microbiota, and immune system in influencing the intestinal barrier function to attenuate the progression of colitis.
Language	English
Publishing date	2023-12-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1291724
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Article: Crescentic Glomerulonephritis: Pathogenesis and Therapeutic Potential of Human Amniotic Stem Cells.

Al Mushafi, Ahmed / Ooi, Joshua D / Odobasic, Dragana

Frontiers in physiology

2021 Volume 12, Page(s) 724186

Abstract: Chronic kidney disease (CKD) leads to significant morbidity and mortality worldwide. Glomerulonephritis (GN) is the second leading cause of CKD resulting in end stage renal failure. The most severe and rapidly progressive type of GN is characterized by ... ...

Abstract	Chronic kidney disease (CKD) leads to significant morbidity and mortality worldwide. Glomerulonephritis (GN) is the second leading cause of CKD resulting in end stage renal failure. The most severe and rapidly progressive type of GN is characterized by glomerular crescent formation. The current therapies for crescentic GN, which consist of broad immunosuppressive drugs, are partially effective, non-specific, toxic and cause many serious side effects including infections, cancer, and cardiovascular problems. Therefore, new and safer therapies are needed. Human amniotic epithelial cells (hAECs) are a type of stem cell which are isolated from the placenta after birth. They represent an attractive and novel therapeutic option for the treatment of various inflammatory conditions owing to their unique and selective immunosuppressive ability, as well as their excellent safety profile and clinical applicability. In this review, we will discuss the immunopathogenesis of crescentic GN, issues with currently available treatments and how hAECs offer potential to become a new and harmless treatment option for this condition.
Language	English
Publishing date	2021-10-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.724186
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Article ; Online: Treg Enhancing Therapies to Treat Autoimmune Diseases.

Eggenhuizen, Peter J / Ng, Boaz H / Ooi, Joshua D

International journal of molecular sciences

2020 Volume 21, Issue 19

Abstract: Regulatory T cells (Tregs) are a small yet critical subset of CD4+ T cells, which have the role of maintaining immune homeostasis by, for example, regulating self-tolerance, tumor immunity, anti-microbial resistance, allergy and transplantation rejection. ...

Abstract	Regulatory T cells (Tregs) are a small yet critical subset of CD4+ T cells, which have the role of maintaining immune homeostasis by, for example, regulating self-tolerance, tumor immunity, anti-microbial resistance, allergy and transplantation rejection. The suppressive mechanisms by which Tregs function are varied and pleiotropic. The ability of Tregs to maintain self-tolerance means they are critical for the control and prevention of autoimmune diseases. Irregularities in Treg function and number can result in loss of tolerance and autoimmune disease. Restoring immune homeostasis and tolerance through the promotion, activation or delivery of Tregs has emerged as a focus for therapies aimed at curing or controlling autoimmune diseases. Such therapies have focused on the Treg cell subset by using drugs to suppress T effector cells and promote Tregs. Other approaches have trialed inducing tolerance by administering the autoantigen via direct administration, by transient expression using a DNA vector, or by antigen-specific nanoparticles. More recently, cell-based therapies have been developed as an approach to directly or indirectly enhance Treg cell specificity, function and number. This can be achieved indirectly by transfer of tolerogenic dendritic cells, which have the potential to expand antigen-specific Treg cells. Treg cells can be directly administered to treat autoimmune disease by way of polyclonal Tregs or Tregs transduced with a receptor with high affinity for the target autoantigen, such as a high affinity T cell receptor (TCR) or a chimeric antigen receptor (CAR). This review will discuss the strategies being developed to redirect autoimmune responses to a state of immune tolerance, with the aim of the prevention or amelioration of autoimmune disease.
MeSH term(s)	Adoptive Transfer ; Animals ; Autoantigens/genetics ; Autoantigens/immunology ; Autoimmune Diseases/genetics ; Autoimmune Diseases/immunology ; Autoimmune Diseases/therapy ; Autoimmunity ; Humans ; Immune Tolerance ; Nanoparticles/therapeutic use ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/transplantation
Chemical Substances	Autoantigens
Language	English
Publishing date	2020-09-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21197015
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Article ; Online: Antigen-driven CD4

Eggenhuizen, Peter J / Ng, Boaz H / Ooi, Joshua D

Immunology and cell biology

2020 Volume 99, Issue 3, Page(s) 252–254

Abstract: In their recent publication, Kuczma and colleagues have provided evidence that advances the relationship between naive T cells, T cell anergy and T regulatory cells. Their findings strengthen the understanding of how these T cell subsets function in ... ...

Abstract	In their recent publication, Kuczma and colleagues have provided evidence that advances the relationship between naive T cells, T cell anergy and T regulatory cells. Their findings strengthen the understanding of how these T cell subsets function in relation to self and microbiota-derived epitopes to promote and maintain peripheral tolerance to self and mucosal antigens.
MeSH term(s)	Antigens ; CD4-Positive T-Lymphocytes ; Clonal Anergy ; T-Lymphocyte Subsets ; T-Lymphocytes, Regulatory
Chemical Substances	Antigens
Language	English
Publishing date	2020-12-04
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12424
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Article ; Online: Editorial: Autoimmune Vasculitis - Advances in Pathogenesis and Therapies.

Ooi, Joshua D / Deng, Jun / De Souza, Alexandre W S

Frontiers in immunology

2021 Volume 12, Page(s) 720257

MeSH term(s)	Animals ; Autoimmune Diseases/diagnosis ; Autoimmune Diseases/etiology ; Autoimmune Diseases/therapy ; Disease Management ; Disease Susceptibility ; Humans ; Vasculitis/diagnosis ; Vasculitis/etiology ; Vasculitis/therapy
Language	English
Publishing date	2021-06-18
Publishing country	Switzerland
Document type	Editorial ; Introductory Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.720257
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Article ; Online: Renal Dendritic Cells: The Long and Winding Road.

Kitching, A Richard / Ooi, Joshua D

Journal of the American Society of Nephrology : JASN

2017 Volume 29, Issue 1, Page(s) 4–7

MeSH term(s)	Dendritic Cells ; Kidney
Language	English
Publishing date	2017-12-11
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2017101145
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Zs.A 3344: Show issues

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Article ; Online: From bench to pet shop to bedside? The environment and immune function in mice.

Kitching, A Richard / Ooi, Joshua D

Kidney international

2016 Volume 90, Issue 6, Page(s) 1142–1143

Abstract: The generation of inbred mouse strains in the late 19th and early 20th centuries, coupled with the later establishment of specific pathogen-free animal research facilities created a powerful biological platform for exploration of the immune system in ... ...

Abstract	The generation of inbred mouse strains in the late 19th and early 20th centuries, coupled with the later establishment of specific pathogen-free animal research facilities created a powerful biological platform for exploration of the immune system in health and disease. Studies in this setting have been responsible for huge advances in our understanding of immunobiology and disease, including immune-mediated kidney disease. However, whereas this reductionist and relatively standardized approach allows us to make sense of complex disease biology, it takes place in controlled environments that clearly differ from those that we humans encounter in everyday life. Recent studies comparing the immune systems of wild mice, pet shop mice, and laboratory mice suggest ways in which the murine immune system can be influenced to behave more like the human immune system.
MeSH term(s)	Animals ; Disease Models, Animal ; Humans ; Mice/immunology
Language	English
Publishing date	2016-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2016.08.017
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Zs.A 797: Show issues

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Article ; Online: Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA.

Gong, Yizi / Shen, Chanjuan / Meng, Ting / Lin, Wei / Hu, Xueling / Tang, Rong / Xiong, Qi / Ooi, Joshua D / Eggenhuizen, Peter J / Chen, Jinbiao / Zhou, Ya-Ou / Luo, Hui / Xu, Jia / Liu, Ning / Xiao, Ping / Xiao, Xiangcheng / Zhong, Yong

Clinical and experimental medicine

2024 Volume 24, Issue 1, Page(s) 66

Abstract: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients' ...

Abstract	Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients' clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the "dominant" phenotype in idiopathic double-positive AAV.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Antibodies, Antineutrophil Cytoplasmic ; Myeloblastin ; Prognosis ; Peroxidase ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/therapy ; Recurrence
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Myeloblastin (EC 3.4.21.76) ; Peroxidase (EC 1.11.1.7)
Language	English
Publishing date	2024-04-02
Publishing country	Italy
Document type	Review ; Journal Article
ZDB-ID	2053018-3
ISSN	1591-9528 ; 1591-8890
ISSN (online)	1591-9528
ISSN	1591-8890
DOI	10.1007/s10238-024-01318-y
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Zs.A 5481: Show issues

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Article ; Online: Epithelially Restricted Interferon Epsilon Protects Against Colitis.

de Geus, Eveline D / Volaric, Jennifer S / Matthews, Antony Y / Mangan, Niamh E / Chang, Janet / Ooi, Joshua D / de Weerd, Nicole A / Giles, Edward M / Hertzog, Paul J

Cellular and molecular gastroenterology and hepatology

2023 Volume 17, Issue 2, Page(s) 267–278

Abstract: Background & aims: Type I interferon (T1IFN) signalling is crucial for maintaining intestinal homeostasis. We previously found that the novel T1IFN, IFNε, is highly expressed by epithelial cells of the female reproductive tract, where it protects ... ...

Abstract	Background & aims: Type I interferon (T1IFN) signalling is crucial for maintaining intestinal homeostasis. We previously found that the novel T1IFN, IFNε, is highly expressed by epithelial cells of the female reproductive tract, where it protects against pathogens. Its function has not been studied in the intestine. We hypothesize that IFNε is important in maintaining intestinal homeostasis. Methods: We characterized IFNε expression in mouse and human intestine by immunostaining and studied its function in the dextran sulfate sodium (DSS) colitis model using both genetic knockouts and neutralizing antibody. Results: We demonstrate that IFNε is expressed in human and mouse intestinal epithelium, and expression is lost in inflammation. Furthermore, we show that IFNε limits intestinal inflammation in mouse models. Regulatory T cell (Treg) frequencies were paradoxically decreased in DSS-treated IFNε-/- mice, suggesting a role for IFNε in maintaining the intestinal Treg compartment. Colitis was ameliorated by transfer of wild-type Tregs into IFNε-/- mice. This demonstrates that IFNε supports intestinal Treg function. Conclusions: Overall, we have shown IFNε expression in intestinal epithelium and its critical role in gut homeostasis. Given its known role in the female reproductive tract, we now show IFNε has a protective role across multiple mucosal surfaces.
MeSH term(s)	Humans ; Mice ; Female ; Animals ; Colitis/metabolism ; Intestinal Mucosa/metabolism ; Inflammation/metabolism ; Signal Transduction ; Interferons/metabolism
Chemical Substances	Interferons (9008-11-1)
Language	English
Publishing date	2023-10-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819778-1
ISSN	2352-345X ; 2352-345X
ISSN (online)	2352-345X
ISSN	2352-345X
DOI	10.1016/j.jcmgh.2023.10.006
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