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Article ; Online: NK-like CD8

Roy Chowdhury, Roshni / Valainis, John R / Dubey, Megha / von Boehmer, Lotta / Sola, Elsa / Wilhelmy, Julie / Guo, Jing / Kask, Oliver / Ohanyan, Mane / Sun, Meng / Huang, Huang / Huang, Xianxi / Nguyen, Patricia K / Scriba, Thomas J / Davis, Mark M / Bendall, Sean C / Chien, Yueh-Hsiu

Science immunology

2023 Volume 8, Issue 81, Page(s) eade3525

Abstract: The response of gamma delta (γδ) T cells in the acute versus chronic phases of the same infection is unclear. How γδ T cells function in ... ...

Abstract	The response of gamma delta (γδ) T cells in the acute versus chronic phases of the same infection is unclear. How γδ T cells function in acute
MeSH term(s)	Humans ; Adolescent ; Receptors, Antigen, T-Cell, gamma-delta ; Tuberculosis ; Mycobacterium tuberculosis ; Intraepithelial Lymphocytes ; CD8-Positive T-Lymphocytes
Chemical Substances	Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.ade3525
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Article ; Online: γδ T cell antigen receptor polyspecificity enables T cell responses to a broad range of immune challenges.

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 4, Page(s) e2315592121

Abstract: γδ T cells are essential for immune defense and modulating physiological processes. While they have the potential to recognize large numbers of antigens through somatic gene rearrangement, the antigens which trigger most γδ T cell response remain ... ...

Abstract	γδ T cells are essential for immune defense and modulating physiological processes. While they have the potential to recognize large numbers of antigens through somatic gene rearrangement, the antigens which trigger most γδ T cell response remain unidentified, and the role of antigen recognition in γδ T cell function is contentious. Here, we show that some γδ T cell receptors (TCRs) exhibit polyspecificity, recognizing multiple ligands of diverse molecular nature. These ligands include haptens, metabolites, neurotransmitters, posttranslational modifications, as well as peptides and proteins of microbial and host origin. Polyspecific γδ T cells are enriched among activated cells in naive mice and the responding population in infection. They express diverse TCR sequences, have different functional potentials, and include the innate-like γδ T cells, such as the major IL-17 responders in various pathological/physiological conditions. We demonstrate that encountering their antigenic microbiome metabolite maintains their homeostasis and functional response, indicating that their ability to recognize multiple ligands is essential for their function. Human γδ T cells with similar polyspecificity also respond to various immune challenges. This study demonstrates that polyspecificity is a prevalent feature of γδ T cell antigen recognition, which enables rapid and robust T cell responses to a wide range of challenges, highlighting a unique function of γδ T cells.
MeSH term(s)	Humans ; Mice ; Animals ; Receptors, Antigen, T-Cell, gamma-delta ; Antigens ; Haptens ; Blood Group Antigens
Chemical Substances	Receptors, Antigen, T-Cell, gamma-delta ; Antigens ; Haptens ; Blood Group Antigens
Language	English
Publishing date	2024-01-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2315592121
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Article ; Online: Synthetic adjuvants for vaccine formulations: phytol derivatives.

Ghosh, Swapan K / Chowdhury, Roshni Roy

Expert opinion on drug delivery

2013 Volume 10, Issue 4, Page(s) 437–450

Abstract: Introduction: The development of vaccines is considered a key milestone in preventive medicine. There is no comparable cost-effective means for controlling or eradicating infectious diseases. Yet, a persistent societal problem is the concern about ... ...

Abstract	Introduction: The development of vaccines is considered a key milestone in preventive medicine. There is no comparable cost-effective means for controlling or eradicating infectious diseases. Yet, a persistent societal problem is the concern about vaccine's safety and long-term effects, and this caters to detractors of vaccination. Pathogen-derived antigen(s) as well as adjuvants/immunostimulants are essential for vaccine efficacy. Currently, adjuvant selection is largely empirical, but the mechanism underlying adjuvanticity is beginning to unravel. This should help develop more defined or targeted adjuvants. Areas covered: This review provides a brief account and analysis of the host immune parameters modulated by some commonly used as well as new adjuvants, including phytol-based diterpenoids. The major efforts are directed toward evaluating their relative safety and immunomodulatory efficiency, compared to known synthetic and natural adjuvants. Concerns for adverse pathological inflammation and autoimmunity are also addressed. Expert opinion: The phytol-based adjuvants hold great promise for improving vaccine efficacy, as they cause little or no persistent inflammation, but are highly effective in stimulating a multifaceted immune response, characterized by proficient recruitment of immune cells, generation of antibody and immunological memory, and activation of both Th1 and Th2 responses. Future focus will be on developing cocktail adjuvants to activate the complement system, mobilize follicular T helper cells as well as NKT and γδ T cells and activate cross-presenting dendritic cells to stimulate CD8(+) effector T cells.
MeSH term(s)	Adjuvants, Immunologic/chemistry ; Chemistry, Pharmaceutical ; Diterpenes/chemistry ; Humans ; Phytol/analogs & derivatives ; Phytol/chemistry ; T-Lymphocytes, Helper-Inducer/immunology ; Vaccination ; Vaccines/chemistry ; Vaccines/immunology
Chemical Substances	Adjuvants, Immunologic ; Diterpenes ; Vaccines ; Phytol (150-86-7)
Language	English
Publishing date	2013-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2167286-6
ISSN	1744-7593 ; 1742-5247
ISSN (online)	1744-7593
ISSN	1742-5247
DOI	10.1517/17425247.2013.757591
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Article ; Online: Phytol-derived novel isoprenoid immunostimulants.

Chowdhury, Roshni Roy / Ghosh, Swapan K

Frontiers in immunology

2012 Volume 3, Page(s) 49

Abstract: This review describes the adjuvanticity of novel diterpenoids (synthetic phytol derivatives) compared to some commercially available adjuvants. The efficacy of the phytol-derived immunostimulants was evaluated in terms of their ability to activate innate ...

Abstract	This review describes the adjuvanticity of novel diterpenoids (synthetic phytol derivatives) compared to some commercially available adjuvants. The efficacy of the phytol-derived immunostimulants was evaluated in terms of their ability to activate innate immunity, amplify various antigen-specific immune responses, and engender immunological memory with no discernible adverse effects in both competent and immune-deficient mice. The profile that emerges out of these studies reveals that the phytol derivatives are excellent immunostimulants, superior to a number of commercial adjuvants in terms of long-term memory induction and activation of both innate and acquired immunity. Additionally, the phytol-derived compounds have no cumulative inflammatory or toxic effects even in immuno-compromised mice.
Language	English
Publishing date	2012-03-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2012.00049
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Article ; Online: Select sequencing of clonally expanded CD8

Huang, Huang / Sikora, Michael J / Islam, Saiful / Chowdhury, Roshni Roy / Chien, Yueh-Hsiu / Scriba, Thomas J / Davis, Mark M / Steinmetz, Lars M

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 18, Page(s) 8995–9001

Abstract: To permit the recognition of antigens, T cells generate a vast diversity of T cell receptor (TCR) sequences. Upon binding of the TCR to an antigen-MHC complex, T cells clonally expand to establish an immune response. To study antigen-specific T cell ... ...

Abstract	To permit the recognition of antigens, T cells generate a vast diversity of T cell receptor (TCR) sequences. Upon binding of the TCR to an antigen-MHC complex, T cells clonally expand to establish an immune response. To study antigen-specific T cell clonality, we have developed a method that allows selection of rare cells, based on RNA expression, before in-depth scRNA-seq (named SELECT-seq). We applied SELECT-seq to collect both TCR sequences and then transcriptomes from single cells of peripheral blood lymphocytes activated by a
MeSH term(s)	Antigens/metabolism ; Base Sequence/genetics ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Clonal Selection, Antigen-Mediated/physiology ; Cytokines/metabolism ; Humans ; Lymphocyte Activation/genetics ; Lymphocyte Activation/physiology ; Mucosal-Associated Invariant T Cells/immunology ; Natural Killer T-Cells/immunology ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/isolation & purification ; Sequence Analysis ; Sequence Analysis, RNA/methods
Chemical Substances	Antigens ; Cytokines ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2019-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1902649116
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Article ; Online: Efficacy of phytol-derived diterpenoid immunoadjuvants over alum in shaping the murine host's immune response to Staphylococcus aureus.

Roy Chowdhury, Roshni / Fitch, Richard W / Ghosh, Swapan K

Vaccine

2013 Volume 31, Issue 8, Page(s) 1178–1186

Abstract: The ubiquitous gram-positive bacterium Staphylococcus aureus occupies a unique niche in humans for its ability to survive both as a commensal and a life-threatening pathogen. Its complex relationship with the host and its ability to engender a throng of ... ...

Abstract	The ubiquitous gram-positive bacterium Staphylococcus aureus occupies a unique niche in humans for its ability to survive both as a commensal and a life-threatening pathogen. Its complex relationship with the host and its ability to engender a throng of virulence factors, have hindered the development of a successful vaccine against it. The use of immunoadjuvants to enhance host immunity and prevent the shift from commensalism to pathogenicity is a rational approach for containing infection. The objective of this study was to understand the mechanisms by which alum and two phytol-derived immunoadjuvants, phytanol (PHIS-01)(1) and phytanyl chloride (PCl)(2) shape the interaction between S. aureus and its murine host. We studied the effects of the phytol derivatives, relative to alum, on the induction of inflammatory cytokines and chemokines, recruitment of CD11b(+) cells, generation of specific anti-S. aureus antibodies and in vitro clearance of S. aureus. Our results showed that both PHIS-01 and PCl were stronger inducers of protective cytokines IL-17 and IL-1β than alum, and far exceeded alum in enhancing anti-S. aureus antibody response. However, both alum and the phytol derivatives (particularly PCl) promoted efficient recruitment of CD11b(+) cells. Furthermore, PHIS-01, alum and to a lesser extent, PCl were able to up-regulate the expression of key inflammation-related genes that were highly down-regulated by S. aureus alone. In vitro killing assays showed that both PHIS-01 and PCl were far more potent than alum in promoting S. aureus clearance; this indicated their efficiency in shaping an effective anti-S. aureus immune microenvironment. In summary, our study provides evidence for the better effectiveness of phytol-derived immunoadjuvants over alum in enhancing anti-S. aureus immunity.
MeSH term(s)	Adjuvants, Immunologic/administration & dosage ; Alum Compounds/administration & dosage ; Animals ; Antibodies, Bacterial/blood ; Cytokines/secretion ; Diterpenes/administration & dosage ; Female ; Mice ; Mice, Inbred BALB C ; Phytol/administration & dosage ; Staphylococcal Infections/immunology ; Staphylococcal Infections/prevention & control ; Staphylococcal Vaccines/administration & dosage ; Staphylococcal Vaccines/immunology ; Staphylococcus aureus/immunology ; T-Lymphocytes/immunology ; Vaccines, Inactivated/administration & dosage ; Vaccines, Inactivated/immunology
Chemical Substances	Adjuvants, Immunologic ; Alum Compounds ; Antibodies, Bacterial ; Cytokines ; Diterpenes ; Staphylococcal Vaccines ; Vaccines, Inactivated ; Phytol (150-86-7) ; aluminum sulfate (34S289N54E)
Language	English
Publishing date	2013-02-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2012.12.069
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Article ; Online: Effects of small intestinal submucosa (SIS) on the murine innate immune microenvironment induced by heat-killed Staphylococcus aureus.

Roy Chowdhury, Roshni / Aachoui, Youssef / Ghosh, Swapan K

PloS one

2012 Volume 7, Issue 11, Page(s) e48724

Abstract: The use of biological scaffold materials for wound healing and tissue remodeling has profoundly impacted regenerative medicine and tissue engineering. The porcine-derived small intestinal submucosa (SIS) is a licensed bioscaffold material regularly used ... ...

Abstract	The use of biological scaffold materials for wound healing and tissue remodeling has profoundly impacted regenerative medicine and tissue engineering. The porcine-derived small intestinal submucosa (SIS) is a licensed bioscaffold material regularly used in wound and tissue repair, often in contaminated surgical fields. Complications and failures due to infection of this biomaterial have therefore been a major concern and challenge. SIS can be colonized and infected by wound-associated bacteria, particularly Staphylococcus aureus. In order to address this concern and develop novel intervention strategies, the immune microenvironment orchestrated by the combined action of S. aureus and SIS should be critically evaluated. Since the outcome of tissue remodeling is largely controlled by the local immune microenvironment, we assessed the innate immune profile in terms of cytokine/chemokine microenvironment and inflammasome-responsive genes. BALB/c mice were injected intra-peritoneally with heat-killed S. aureus in the presence or absence of SIS. Analyses of cytokines, chemokines and microarray profiling of inflammasome-related genes were done using peritoneal lavages collected 24 hours after injection. Results showed that unlike SIS, the S. aureus-SIS interactome was characterized by a Th1-biased immune profile with increased expressions of IFN-γ, IL-12 and decreased expressions of IL-4, IL-13, IL-33 and IL-6. Such modulation of the Th1/Th2 axis can greatly facilitate graft rejections. The S. aureus-SIS exposure also augmented the expressions of pro-inflammatory cytokines like IL-1β, Tnf-α, CD30L, Eotaxin and Fractalkine. This heightened inflammatory response caused by S. aureus contamination could enormously affect the biocompatibility of SIS. However, the mRNA expressions of many inflammasome-related genes like Nlrp3, Aim2, Card6 and Pycard were down-regulated by heat-killed S. aureus with or without SIS. In summary, our study explored the innate immune microenvironment induced by the combined exposure of SIS and S. aureus. These results have practical implications in developing strategies to contain infection and promote successful tissue repair.
MeSH term(s)	Animals ; CD30 Ligand/metabolism ; Cellular Microenvironment/genetics ; Cellular Microenvironment/immunology ; Chemokine CX3CL1/immunology ; Chemokine CX3CL1/metabolism ; Chemokines, CC/immunology ; Chemokines, CC/metabolism ; Cytokines/immunology ; Cytokines/metabolism ; Female ; Gene Expression Regulation ; Guided Tissue Regeneration ; Immunity, Innate/genetics ; Inflammasomes/genetics ; Inflammasomes/immunology ; Inflammation Mediators/immunology ; Inflammation Mediators/metabolism ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestine, Small/immunology ; Intestine, Small/metabolism ; Mice ; Models, Biological ; Staphylococcus aureus/immunology ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Th2 Cells/immunology ; Th2 Cells/metabolism ; Wound Healing/immunology
Chemical Substances	CD30 Ligand ; Chemokine CX3CL1 ; Chemokines, CC ; Cytokines ; Inflammasomes ; Inflammation Mediators
Language	English
Publishing date	2012-11-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0048724
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Article ; Online: Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab.

Allergy

2021 Volume 76, Issue 9, Page(s) 2809–2826

Abstract: Background: Multifood oral immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, XOLAIR: Methods: Participants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the ... ...

Abstract	Background: Multifood oral immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, XOLAIR Methods: Participants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the immune profile of PBMCs and plasma taken at baseline, week 8, and week 36 using high-dimensional mass cytometry, component-resolved diagnostics, the indirect basophil activation test, and Luminex. Results: We found (i) decreased frequency of IL-4 Conclusions: This exploratory study provides novel comprehensive insight into the immune underpinnings of desensitization through omalizumab-facilitated mOIT. Moreover, this study provides encouraging results to support the complex immune changes that can be induced by OIT.
MeSH term(s)	Administration, Oral ; Allergens ; Desensitization, Immunologic ; Humans ; Immunoglobulin E ; Omalizumab/therapeutic use ; Peanut Hypersensitivity
Chemical Substances	Allergens ; Omalizumab (2P471X1Z11) ; Immunoglobulin E (37341-29-0)
Language	English
Publishing date	2021-05-29
Publishing country	Denmark
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.14833
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Article ; Online: Effects of small intestinal submucosa (SIS) on the murine innate immune microenvironment induced by heat-killed Staphylococcus aureus.

Roshni Roy Chowdhury / Youssef Aachoui / Swapan K Ghosh

PLoS ONE, Vol 7, Iss 11, p e

2012 Volume 48724

Abstract	The use of biological scaffold materials for wound healing and tissue remodeling has profoundly impacted regenerative medicine and tissue engineering. The porcine-derived small intestinal submucosa (SIS) is a licensed bioscaffold material regularly used in wound and tissue repair, often in contaminated surgical fields. Complications and failures due to infection of this biomaterial have therefore been a major concern and challenge. SIS can be colonized and infected by wound-associated bacteria, particularly Staphylococcus aureus. In order to address this concern and develop novel intervention strategies, the immune microenvironment orchestrated by the combined action of S. aureus and SIS should be critically evaluated. Since the outcome of tissue remodeling is largely controlled by the local immune microenvironment, we assessed the innate immune profile in terms of cytokine/chemokine microenvironment and inflammasome-responsive genes. BALB/c mice were injected intra-peritoneally with heat-killed S. aureus in the presence or absence of SIS. Analyses of cytokines, chemokines and microarray profiling of inflammasome-related genes were done using peritoneal lavages collected 24 hours after injection. Results showed that unlike SIS, the S. aureus-SIS interactome was characterized by a Th1-biased immune profile with increased expressions of IFN-γ, IL-12 and decreased expressions of IL-4, IL-13, IL-33 and IL-6. Such modulation of the Th1/Th2 axis can greatly facilitate graft rejections. The S. aureus-SIS exposure also augmented the expressions of pro-inflammatory cytokines like IL-1β, Tnf-α, CD30L, Eotaxin and Fractalkine. This heightened inflammatory response caused by S. aureus contamination could enormously affect the biocompatibility of SIS. However, the mRNA expressions of many inflammasome-related genes like Nlrp3, Aim2, Card6 and Pycard were down-regulated by heat-killed S. aureus with or without SIS. In summary, our study explored the innate immune microenvironment induced by the combined exposure of SIS and S. ...
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self.

Chowdhury, Roshni Roy / D'Addabbo, Jessica / Huang, Xianxi / Veizades, Stefan / Sasagawa, Koki / Louis, David M / Cheng, Paul / Sokol, Jan / Jensen, Annie / Tso, Alexandria / Shankar, Vishnu / Wendel, Ben Shogo / Bakerman, Isaac / Liang, Grace / Koyano, Tiffany / Fong, Robyn / Nau, Allison N / Ahmad, Herra / Gopakumar, Jayakrishnan /

Wirka, Robert / Lee, Andrew S / Boyd, Jack / Woo, Y Joseph / Quertermous, Thomas / Gulati, Gunsagar Singh / Jaiswal, Siddhartha / Chien, Yueh-Hsiu / Chan, Charles Kwok Fai / Davis, Mark M / Nguyen, Patricia K

Circulation research

2022 Volume 130, Issue 10, Page(s) 1510–1530

Abstract: Background: Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation' notable for the buildup of ... ...

Abstract	Background: Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation' notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies. Methods: We used single-cell technology and in vitro assays to interrogate the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. Results: In addition to macrophages, we found a high proportion of αβ T cells in the coronary plaques. Most of these T cells lack high expression of Conclusions: Taken together, these findings demonstrate that plaque T cells are clonally expanded potentially by antigen engagement, are potentially reactive to self-epitopes, and may interact with smooth muscle cells and macrophages in the plaque microenvironment.
MeSH term(s)	Antigens ; Clone Cells/immunology ; Coronary Artery Disease/immunology ; Endothelial Cells ; Epitopes ; HLA-DR alpha-Chains ; Humans ; Lymphocyte Activation ; Plaque, Atherosclerotic/immunology ; T-Lymphocytes/immunology
Chemical Substances	Antigens ; Epitopes ; HLA-DR alpha-Chains
Language	English
Publishing date	2022-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.121.320090
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