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Article ; Online: CD8+ T cells: The past and future of immune regulation.

Lees, Jason R

2020 Volume 357, Page(s) 104212

Abstract: Regulation of the adaptive immune response is critical for health. Regulatory activity can be found in multiple components of the immune system, however, the focus on particular components of the immune regulatory network has left many aspects of this ... ...

Abstract	Regulation of the adaptive immune response is critical for health. Regulatory activity can be found in multiple components of the immune system, however, the focus on particular components of the immune regulatory network has left many aspects of this critical immune component understudied. Here we review the evidence for activities of CD8+ T cells in immune homeostasis and regulation of autoimmune reactivity. The heterogeneous nature of identified CD8+ cell types are examined, and common phenotypes associated with functional activities are defined. The varying types of antigen signal crucial for CD8+ T cell regulatory activity are identified and the implications of these activation pathways for control of adaptive responses is considered. Finally, the promising capacity for transgenic antigen receptor directed cytotoxicity as a mechanism for modulation of autoimmunity is detailed.
MeSH term(s)	Adaptive Immunity/immunology ; Animals ; Autoimmunity/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/physiology ; Humans ; Immune Tolerance/immunology ; Immune Tolerance/physiology ; T-Lymphocytes, Regulatory/immunology
Language	English
Publishing date	2020-09-04
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	80094-6
ISSN	1090-2163 ; 0008-8749
ISSN (online)	1090-2163
ISSN	0008-8749
DOI	10.1016/j.cellimm.2020.104212
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Zs.A 417: Show issues

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Article ; Online: Targeting antigen presentation in autoimmunity.

Lees, Jason R

Cellular immunology

2018 Volume 339, Page(s) 4–9

Abstract: Autoimmune diseases are heterogeneous group of disorders that together represent an enormous societal and medical problem. CD4+ T cells have critical roles in the initiation and pathogenesis of autoimmune disease. As such, modulation of T cell activity ... ...

Abstract	Autoimmune diseases are heterogeneous group of disorders that together represent an enormous societal and medical problem. CD4+ T cells have critical roles in the initiation and pathogenesis of autoimmune disease. As such, modulation of T cell activity has proven to have significant therapeutic effects in multiple autoimmune settings. T cell activation is a complex process with multiple potential therapeutic targets, many of which have been successfully utilized to treat human disease. Current pharmacological treatment largely targets T cell intrinsic activities as a means of treating various autoimmune disorders. Here I review extant and potential therapeutic approaches that instead specifically target antigen presentation to CD4+ T cells as a critical checkpoint in autoimmune responses. In addition, the contribution of antigen modulation components in current therapeutic approaches is considered along with the impact of new antigen targeted treatment modalities. Finally, potential challenges are considered in the context of the potential for antigen specific targeting of the antigen presentation process.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigens/immunology ; Autoimmune Diseases/immunology ; Autoimmunity/immunology ; CD4-Positive T-Lymphocytes/immunology ; Humans
Chemical Substances	Antigens
Language	English
Publishing date	2018-12-11
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	80094-6
ISSN	1090-2163 ; 0008-8749
ISSN (online)	1090-2163
ISSN	0008-8749
DOI	10.1016/j.cellimm.2018.12.006
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Zs.A 417: Show issues

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Article ; Online: Interferon gamma in autoimmunity: A complicated player on a complex stage.

Lees, Jason R

Cytokine

2015 Volume 74, Issue 1, Page(s) 18–26

Abstract: Early views of autoimmune disease cast IFNγ as a prototypic pro-inflammatory factor. It is now clear that IFNγ is capable of both pro- and anti-inflammatory activities with the functional outcome dependent on the physiological and pathological setting ... ...

Abstract	Early views of autoimmune disease cast IFNγ as a prototypic pro-inflammatory factor. It is now clear that IFNγ is capable of both pro- and anti-inflammatory activities with the functional outcome dependent on the physiological and pathological setting examined. Here, the major immune modulatory activities of IFNγ are reviewed and current evidence for the impact of IFNγ on pathology and regulation of several autoimmune diseases and disease models is summarized.
MeSH term(s)	Autoimmune Diseases/immunology ; Autoimmunity ; Cytokines/immunology ; Humans ; Immunologic Factors ; Inflammation/immunology ; Interferon-gamma/immunology ; Signal Transduction
Chemical Substances	Cytokines ; Immunologic Factors ; Interferon-gamma (82115-62-6)
Keywords	covid19
Language	English
Publishing date	2015-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2014.10.014
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Zs.A 2840: Show issues

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Article ; Online: High K

Packialakshmi, Balamurugan / Hira, Sharanpreet / Feng, Yuanyi / Scott, David W / Lees, Jason R / Zhou, Xiaoming

Cellular immunology

2022 Volume 382, Page(s) 104637

Abstract: Multiple sclerosis is believed to be triggered by the interplay between the environmental and genetic factors. In contrast to the Paleolithic diet, the modern Western diet is high in ... ...

Abstract	Multiple sclerosis is believed to be triggered by the interplay between the environmental and genetic factors. In contrast to the Paleolithic diet, the modern Western diet is high in Na
MeSH term(s)	Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental ; T-Lymphocytes, Regulatory ; Th17 Cells ; Mice, Inbred C57BL ; Multiple Sclerosis
Language	English
Publishing date	2022-11-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80094-6
ISSN	1090-2163 ; 0008-8749
ISSN (online)	1090-2163
ISSN	0008-8749
DOI	10.1016/j.cellimm.2022.104637
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Zs.A 417: Show issues

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Article ; Online: Perspectives on elder mistreatment screening and responding in emergency departments: A qualitative study with survivors.

Burnett, Jason / Campetti, Randi / Froberg, Ruthann / Beauchamp, Jennifer Es / Lees-Haggerty, Kristin

International journal of psychiatry in medicine

2024 , Page(s) 912174231225765

Abstract: Objective: Elder Mistreatment (EM) occurs in approximately 10% of older adults and is associated with trauma-related outcomes including depression, anxiety, post-traumatic stress disorder, and early mortality. Low screening and older adult self- ... ...

Abstract	Objective: Elder Mistreatment (EM) occurs in approximately 10% of older adults and is associated with trauma-related outcomes including depression, anxiety, post-traumatic stress disorder, and early mortality. Low screening and older adult self-reporting rates, especially within Emergency Departments represent missed opportunities for identify and mitigate future EM occurrences and consequences. To date, no studies have obtained EM survivors perspectives of EM screening and response practices in emergency departments. Methods: Semi-structured interviews with 19 EM survivors with Adult Protective Services validated EM were completed in the older adult's home. The Elder Mistreatment Emergency Department Screening and Response Tool (EM-SART) was used to guide the interview questions. All interviews were recorded, transcribed, and analyzed using qualitative thematic analyses. Results: The participants were mostly female (63%) and white (58%) with an average age of 74 years. Physical abuse accounted for 67% of the EM incidents. Three themes emerged indicating the survivor preference for (1) building rapport and approaching the older adult with compassion and care, (2) setting the context before asking the EM questions, and (3) allowing mutuality, collaborative work, and shared decision-making during the response. Conclusions: Older adults are agreeable and willing to self-report and actively engage in the EM screening and response practices in the emergency department if trauma-informed care principles are utilized.
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	220669-9
ISSN	1541-3527 ; 0091-2174
ISSN (online)	1541-3527
ISSN	0091-2174
DOI	10.1177/00912174231225765
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Article ; Online: NFAT5 contributes to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and decrease of T regulatory cells in female mice.

Packialakshmi, Balamurugan / Hira, Sharanpreet / Lund, Kateryna / Zhang, Ai-Hong / Halterman, Julia / Feng, Yuanyi / Scott, David W / Lees, Jason R / Zhou, Xiaoming

Cellular immunology

2022 Volume 375, Page(s) 104515

Abstract: Multiple sclerosis disproportionally affects women. The present study was undertaken to determine whether NFAT5 contributed to the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, and if it did, whether the ... ...

Abstract	Multiple sclerosis disproportionally affects women. The present study was undertaken to determine whether NFAT5 contributed to the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, and if it did, whether the impact was sex associated. NFAT5 haplodeficiency reduced the disease severity only in female mice. This effect was associated with significant increases in frequency of T regulatory (Treg) cells in the CNS (from 1.45 ± 0.39% to 3.73 ± 0.94%) and spleen from (0.31 ± 0.06% to 0.94 ± 0.29%) without significantly affecting the CNS CD4
MeSH term(s)	Animals ; Encephalomyelitis, Autoimmune, Experimental/genetics ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Female ; Humans ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis ; Spleen ; T-Lymphocytes, Regulatory ; Transcription Factors/genetics
Chemical Substances	Nfat5 protein, mouse ; Transcription Factors
Language	English
Publishing date	2022-04-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80094-6
ISSN	1090-2163 ; 0008-8749
ISSN (online)	1090-2163
ISSN	0008-8749
DOI	10.1016/j.cellimm.2022.104515
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Zs.A 417: Show issues

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Article ; Online: Engineering CRISPR/Cas9 for Multiplexed Recombinant Coagulation Factor Production.

Feser, Colby J / Lees, Christopher J / Lammers, Daniel T / Riddle, Megan J / Bingham, Jason R / Eckert, Matthew J / Tolar, Jakub / Osborn, Mark J

International journal of molecular sciences

2022 Volume 23, Issue 9

Abstract: Current hemostatic agents are obtained from pooled plasma from multiple donors requiring costly pathogen screening and processing. Recombinant DNA-based production represents an engineering solution that could improve supply, uniformity, and safety. ... ...

Abstract	Current hemostatic agents are obtained from pooled plasma from multiple donors requiring costly pathogen screening and processing. Recombinant DNA-based production represents an engineering solution that could improve supply, uniformity, and safety. Current approaches are typically for single gene candidate peptides and often employ non-human cells. We devised an approach where multiple gene products could be produced from a single population of cells. We identified gene specific Synergistic Activation Mediators (SAM) from the CRISPR/Cas9 system for targeted overexpression of coagulation factors II, VII, IX, X, and fibrinogen. The components of the CRISPR-SAM system were expressed in Human Embryonic Kidney Cells (HEK293), and single (singleplex) or multi-gene (multiplex) upregulation was assessed by quantitative RT-PCR (qRT-PCR) and protein expression by ELISA analysis. Factor II, VII, IX, and X singleplex and multiplex activation resulted in 120-4700-fold and 60-680-fold increases in gene expression, respectively. Fibrinogen sub-unit gene activation resulted in a 1700-92,000-fold increases and 80-5500-fold increases in singleplex or multiplex approaches, respectively. ELISA analysis showed a concomitant upregulation of candidate gene products. Our findings demonstrate the capability of CRISPR/Cas9 SAMs for single or multi-agent production in human cells and represent an engineering advance that augments current recombinant peptide production techniques.
MeSH term(s)	Blood Coagulation Factors/biosynthesis ; Blood Coagulation Factors/genetics ; CRISPR-Cas Systems ; Fibrinogen/genetics ; Gene Editing/methods ; HEK293 Cells ; Humans ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Transcriptional Activation
Chemical Substances	Blood Coagulation Factors ; Recombinant Proteins ; Fibrinogen (9001-32-5)
Language	English
Publishing date	2022-05-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23095090
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Article ; Online: A novel CNS-homing peptide for targeting neuroinflammatory lesions in experimental autoimmune encephalomyelitis.

Acharya, Bodhraj / Meka, Rakeshchandra R / Venkatesha, Shivaprasad H / Lees, Jason R / Teesalu, Tambet / Moudgil, Kamal D

Molecular and cellular probes

2020 Volume 51, Page(s) 101530

Abstract: Using phage peptide library screening, we identified peptide-encoding phages that selectively home to the inflamed central nervous system (CNS) of mice with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis (MS). A ... ...

Abstract	Using phage peptide library screening, we identified peptide-encoding phages that selectively home to the inflamed central nervous system (CNS) of mice with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis (MS). A phage peptide display library encoding cyclic 9-amino-acid random peptides was first screened ex-vivo for binding to the CNS tissue of EAE mice, followed by in vivo screening in the diseased mice. Phage insert sequences that were present at a higher frequency in the CNS of EAE mice than in the normal (control) mice were identified by DNA sequencing. One of the phages selected in this manner, denoted as MS-1, was shown to selectively recognize CNS tissue in EAE mice. Individually cloned phages with this insert preferentially homed to EAE CNS after an intravenous injection. Similarly, systemically-administered fluorescence-labeled synthetic MS-1 peptide showed selective accumulation in the spinal cord of EAE mice. We suggest that peptide MS-1 might be useful for targeted drug delivery to CNS in EAE/MS.
MeSH term(s)	Animals ; Brain/metabolism ; Central Nervous System/metabolism ; Computational Biology ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Encephalomyelitis, Autoimmune, Experimental/pathology ; High-Throughput Nucleotide Sequencing ; Inflammation/metabolism ; Mice ; Mice, Inbred C57BL ; Peptide Library ; Peptides/genetics ; Peptides/metabolism ; Spinal Cord/metabolism
Chemical Substances	Peptide Library ; Peptides
Language	English
Publishing date	2020-02-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639082-1
ISSN	1096-1194 ; 0890-8508
ISSN (online)	1096-1194
ISSN	0890-8508
DOI	10.1016/j.mcp.2020.101530
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Zs.A 2230: Show issues

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Article ; Online: Addendum: Synthesis and reactivity of precolibactin 886.

Healy, Alan R / Wernke, Kevin M / Kim, Chung Sub / Lees, Nicholas R / Crawford, Jason M / Herzon, Seth B

Nature chemistry

2019 Volume 11, Issue 12, Page(s) 1167

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Language	English
Publishing date	2019-11-12
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2464596-5
ISSN	1755-4349 ; 1755-4330
ISSN (online)	1755-4349
ISSN	1755-4330
DOI	10.1038/s41557-019-0383-x
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Article ; Online: Pre-existing central nervous system lesions negate cytokine requirements for regional experimental autoimmune encephalomyelitis development.

Li, Xin / Lees, Jason R

Immunology

2012 Volume 138, Issue 3, Page(s) 208–215

Abstract: In region-specific forms of experimental autoimmune encephalomyelitis (EAE), lesion initiation is regulated by T-cell-produced interferon-γ (IFN-γ) resulting in spinal cord disease in the presence of IFN-γ and cerebellar disease in the absence of IFN-γ. ... ...

Abstract	In region-specific forms of experimental autoimmune encephalomyelitis (EAE), lesion initiation is regulated by T-cell-produced interferon-γ (IFN-γ) resulting in spinal cord disease in the presence of IFN-γ and cerebellar disease in the absence of IFN-γ. Although this role for IFN-γ in regional disease initiation is well defined, little is known about the consequences of previous tissue inflammation on subsequent regional disease, information vital to the development of therapeutics in established disease states. This study addressed the hypothesis that previous establishment of regional EAE would determine subsequent tissue localization of new T-cell invasion and associated symptoms regardless of the presence or absence of IFN-γ production. Serial transfer of optimal or suboptimal doses of encephalitogenic IFN-γ-sufficient or -deficient T-cell lines was used to examine the development of new clinical responses associated with the spinal cord and cerebellum at various times after EAE initiation. Previous inflammation within either cerebellum or spinal cord allowed subsequent T-cell driven inflammation within that tissue regardless of IFN-γ presence. Further, T-cell IFN-γ production after initial lesion formation exacerbated disease within the cerebellum, suggesting that IFN-γ plays different roles at different stages of cerebellar disease. For the spinal cord, IFN-γ-deficient cells (that are ordinarily cerebellum disease initiators) were capable of driving new spinal-cord-associated clinical symptoms more than 60 days after the initial acute EAE resolution. These data suggest that previous inflammation modulates the molecular requirements for new neuroinflammation development.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Cell Line ; Cytokines/metabolism ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/genetics ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Humans ; Interferon-gamma/genetics ; Interferon-gamma/metabolism ; Mice ; Mice, Transgenic
Chemical Substances	Cytokines ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2012-12-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.12029
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