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Article ; Online: Type 2 Innate Lymphoid Cells: Protectors in Type 2 Diabetes.

Painter, Jacob D / Akbari, Omid

2021 Volume 12, Page(s) 727008

Abstract: Type 2 innate lymphoid cells (ILC2) are the innate counterparts of Th2 cells and are critically involved in the maintenance of homeostasis in a variety of tissues. Instead of expressing specific antigen receptors, ILC2s respond to external stimuli such ... ...

Abstract	Type 2 innate lymphoid cells (ILC2) are the innate counterparts of Th2 cells and are critically involved in the maintenance of homeostasis in a variety of tissues. Instead of expressing specific antigen receptors, ILC2s respond to external stimuli such as alarmins released from damage. These cells help control the delicate balance of inflammation in adipose tissue, which is a determinant of metabolic outcome. ILC2s play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM) through their protective effects on tissue homeostasis. A variety of crosstalk takes place between resident adipose cells and ILC2s, with each interaction playing a key role in controlling this balance. ILC2 effector function is associated with increased browning of adipose tissue and an anti-inflammatory immune profile. Trafficking and maintenance of ILC2 populations are critical for tissue homeostasis. The metabolic environment and energy source significantly affect the number and function of ILC2s in addition to affecting their interactions with resident cell types. How ILC2s react to changes in the metabolic environment is a clear determinant of the severity of disease. Treating sources of metabolic instability
MeSH term(s)	Adipose Tissue/immunology ; Animals ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/immunology ; Diabetes Mellitus, Type 2/metabolism ; Humans ; Immunity, Innate ; Lymphocytes/immunology ; Lymphocytes/metabolism ; Metabolomics
Language	English
Publishing date	2021-08-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.727008
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Article ; Online: Role of Autophagy in Lung Inflammation.

Painter, Jacob D / Galle-Treger, Lauriane / Akbari, Omid

Frontiers in immunology

2020 Volume 11, Page(s) 1337

Abstract: Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents ... ...

Abstract	Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents are degraded. The maintenance of cellular homeostasis is key in the survival and function of a variety of human cell populations. The interconnection between metabolism and autophagy is extensive, therefore it has a role in a variety of different cell functions. The disruption or dysfunction of autophagy in these cell types have been implicated in the development of a variety of inflammatory diseases including asthma. The role of autophagy in non-immune and immune cells both lead to the pathogenesis of lung inflammation. Autophagy in pulmonary non-immune cells leads to tissue remodeling which can develop into chronic asthma cases with long term effects. The role autophagy in the lymphoid and myeloid lineages in the pathology of asthma differ in their functions. Impaired autophagy in lymphoid populations have been shown, in general, to decrease inflammation in both asthma and inflammatory disease models. Many lymphoid cells rely on autophagy for effector function and maintained inflammation. In stark contrast, autophagy deficient antigen presenting cells have been shown to have an activated inflammasome. This is largely characterized by a T
MeSH term(s)	Animals ; Asthma/complications ; Asthma/immunology ; Asthma/pathology ; Autophagosomes/metabolism ; Autophagy/drug effects ; Autophagy/immunology ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/pathology ; Dendritic Cells/metabolism ; Humans ; Lymphocytes/metabolism ; Lysosomes/metabolism ; Myeloid Cells/metabolism ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Pneumonia, Viral/pathology ; Respiratory Mucosa/metabolism ; SARS-CoV-2 ; Signal Transduction/immunology
Keywords	covid19
Language	English
Publishing date	2020-07-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.01337
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Article ; Online: Adopting the RE-AIM analytic framework for rural program evaluation: experiences from the Advance Care Planning via Group Visits (ACP-GV) national evaluation.

Matthieu, Monica M / Taylor, Laura D / Adkins, David A / Williams, J Silas / Hu, Bo / Oliver, Ciara M / McCullough, Jane Ann / Mallory, Mary J / Smith, Ian D / Painter, Jacob T / Ounpraseuth, Songthip T / Garner, Kimberly K

Frontiers in health services

2024 Volume 4, Page(s) 1210166

Abstract: Introduction: To support rigorous evaluation across a national portfolio of grants, the United States Department of Veterans Affairs (VA) Office of Rural Health (ORH) adopted an analytic framework to guide their grantees' evaluation of initiatives that ... ...

Abstract	Introduction: To support rigorous evaluation across a national portfolio of grants, the United States Department of Veterans Affairs (VA) Office of Rural Health (ORH) adopted an analytic framework to guide their grantees' evaluation of initiatives that reach rural veterans and to standardize the reporting of outcomes and impacts. Advance Care Planning via Group Visits (ACP-GV), one of ORH's Enterprise-Wide Initiatives, also followed the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. ACP-GV is a national patient-centered intervention delivered in a large, veterans integrated healthcare system. This manuscript describes how RE-AIM was used to evaluate this national program and lessons learned from ORH's annual reporting feedback to ACP-GV on their use of the framework to describe evaluation impacts. Methods: We used patient, provider, and site-level administrative health care data from the VA Corporate Data Warehouse and national program management databases for federal fiscal years (FY) spanning October 1, 2018-September 30, 2023. Measures included cumulative and past FY metrics developed to assess program impacts. Results: RE-AIM constructs included the following cumulative and annual program evaluation results. ACP-GV reached 54,167 unique veterans, including 19,032 unique rural veterans between FY 2018 to FY 2023. During FY 2023, implementation adherence to the ACP-GV model was noted in 91.7% of program completers, with 55% of these completers reporting a knowledge increase and 14% reporting a substantial knowledge increase (effectiveness). As of FY 2023, 66 ACP-GV sites were active, and 1,556 VA staff were trained in the intervention (adoption). Of the 66 active sites in FY 2023, 27 were sites previously funded by ORH and continued to offer ACP-GV after the conclusion of three years of seed funding (maintenance). Discussion: Lessons learned developing RE-AIM metrics collaboratively with program developers, implementers, and evaluators allowed for a balance of clinical and scientific input in decision-making, while the ORH annual reporting feedback provided specificity and emphasis for including both cumulative, annual, and rural specific metrics. ACP-GV's use of RE-AIM metrics is a key step towards improving rural veteran health outcomes and describing real world program impacts.
Language	English
Publishing date	2024-03-25
Publishing country	Switzerland
Document type	Journal Article
ISSN	2813-0146
ISSN (online)	2813-0146
DOI	10.3389/frhs.2024.1210166
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Article ; Online: Role of Autophagy in Lung Inflammation

Jacob D. Painter / Lauriane Galle-Treger / Omid Akbari

Frontiers in Immunology, Vol

2020 Volume 11

Abstract	Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents are degraded. The maintenance of cellular homeostasis is key in the survival and function of a variety of human cell populations. The interconnection between metabolism and autophagy is extensive, therefore it has a role in a variety of different cell functions. The disruption or dysfunction of autophagy in these cell types have been implicated in the development of a variety of inflammatory diseases including asthma. The role of autophagy in non-immune and immune cells both lead to the pathogenesis of lung inflammation. Autophagy in pulmonary non-immune cells leads to tissue remodeling which can develop into chronic asthma cases with long term effects. The role autophagy in the lymphoid and myeloid lineages in the pathology of asthma differ in their functions. Impaired autophagy in lymphoid populations have been shown, in general, to decrease inflammation in both asthma and inflammatory disease models. Many lymphoid cells rely on autophagy for effector function and maintained inflammation. In stark contrast, autophagy deficient antigen presenting cells have been shown to have an activated inflammasome. This is largely characterized by a TH17 response that is accompanied with a much worse prognosis including granulocyte mediated inflammation and steroid resistance. The cell specificity associated with changes in autophagic flux complicates its targeting for amelioration of asthmatic symptoms. Differing asthmatic phenotypes between TH2 and TH17 mediated disease may require different autophagic modulations. Therefore, treatments call for a more cell specific and personalized approach when looking at chronic asthma cases. Viral-induced lung inflammation, such as that caused by SARS-CoV-2, also may involve autophagic modulation leading to inflammation mediated by lung resident cells. In this review, we will be discussing the role of autophagy in non-immune cells, myeloid cells, and lymphoid cells for their implications into lung inflammation and asthma. Finally, we will discuss autophagy's role viral pathogenesis, immunometabolism, and asthma with insights into autophagic modulators for amelioration of lung inflammation.
Keywords	autophagy ; asthma ; lung inflammation ; immunometabolism ; COVID-19 ; SARS-CoV-2 ; Immunologic diseases. Allergy ; RC581-607 ; covid19
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: PD-L2 controls peripherally induced regulatory T cells by maintaining metabolic activity and Foxp3 stability.

Hurrell, Benjamin P / Helou, Doumet Georges / Howard, Emily / Painter, Jacob D / Shafiei-Jahani, Pedram / Sharpe, Arlene H / Akbari, Omid

Nature communications

2022 Volume 13, Issue 1, Page(s) 5118

Abstract: Regulatory T (Treg) cells are central to limit immune responses to allergens. Here we show that PD-L2 deficiency prevents the induction of tolerance to ovalbumin and control of airway hyperreactivity, in particular by limiting pTreg numbers and function. ...

Abstract	Regulatory T (Treg) cells are central to limit immune responses to allergens. Here we show that PD-L2 deficiency prevents the induction of tolerance to ovalbumin and control of airway hyperreactivity, in particular by limiting pTreg numbers and function. In vitro, PD-1/PD-L2 interactions increase iTreg numbers and stability. In mice lacking PD-L2 we find lower numbers of splenic pTregs at steady state, producing less IL-10 upon activation and with reduced suppressive activity. Remarkably, the numbers of splenic pTregs are restored by adoptively transferring PD-L2
MeSH term(s)	Animals ; Forkhead Transcription Factors/metabolism ; Interleukin-10/genetics ; Interleukin-10/metabolism ; Mice ; Ovalbumin ; Programmed Cell Death 1 Ligand 2 Protein/metabolism ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/metabolism ; T-Lymphocytes, Regulatory/metabolism
Chemical Substances	Forkhead Transcription Factors ; Foxp3 protein, mouse ; Programmed Cell Death 1 Ligand 2 Protein ; Programmed Cell Death 1 Receptor ; Interleukin-10 (130068-27-8) ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2022-08-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-32899-5
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Article ; Online: Retrospective Cohort Study of Safety Outcomes Associated with Opioid Rotations to Buprenorphine.

Shah, Neil K / Chandler, Michael W / Cetto, Anne V / Luciani, Lisa L / Painter, Jacob / Bailey, Danielle

Journal of pain & palliative care pharmacotherapy

2023 Volume 37, Issue 3, Page(s) 234–245

Abstract: The objective of this study was to understand the effect buprenorphine rotations have on respiratory risk and other safety outcomes. This was a retrospective observational study evaluating Veterans who underwent an opioid rotation from full-agonist ... ...

Abstract	The objective of this study was to understand the effect buprenorphine rotations have on respiratory risk and other safety outcomes. This was a retrospective observational study evaluating Veterans who underwent an opioid rotation from full-agonist opioids to buprenorphine products or to alternative opioids. The primary endpoint was change in the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD) score from baseline to six months post-rotation. Median baseline RIOSORD scores were 26.0 and 18.0 in the Buprenorphine Group and the Alternative Opioid Group, respectively. There was no statistically significant difference between groups in baseline RIOSORD score. At six months post-rotation, median RIOSORD scores were 23.5 and 23.0 in the Buprenorphine Group and Alternative Opioid Group, respectively. The difference in change in RIOSORD scores between groups was not statistically significant (
MeSH term(s)	Humans ; Buprenorphine/adverse effects ; Analgesics, Opioid/adverse effects ; Retrospective Studies ; Pain Management ; Respiratory Insufficiency/chemically induced ; Opioid-Related Disorders/drug therapy
Chemical Substances	Buprenorphine (40D3SCR4GZ) ; Analgesics, Opioid
Language	English
Publishing date	2023-04-25
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2078852-6
ISSN	1536-0539 ; 1536-0288
ISSN (online)	1536-0539
ISSN	1536-0288
DOI	10.1080/15360288.2023.2200412
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Article ; Online: PD-L2 controls peripherally induced regulatory T cells by maintaining metabolic activity and Foxp3 stability

Benjamin P. Hurrell / Doumet Georges Helou / Emily Howard / Jacob D. Painter / Pedram Shafiei-Jahani / Arlene H. Sharpe / Omid Akbari

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 14

Abstract: Regulatory T (Treg) cells have been implicated in the induction of airway tolerance and amelioration of respiratory duct inflammation. Here the authors show, using PD-L2 deficient mice, that the immune suppression signal from PD-L2 is important for ... ...

Abstract	Regulatory T (Treg) cells have been implicated in the induction of airway tolerance and amelioration of respiratory duct inflammation. Here the authors show, using PD-L2 deficient mice, that the immune suppression signal from PD-L2 is important for modulating Treg cell metabolism and function for proper induction of respiratory tolerance in mice.
Keywords	Science ; Q
Language	English
Publishing date	2022-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Role of Autophagy in Lung Inflammation

Painter, Jacob D / Galle-Treger, Lauriane / Akbari, Omid

Front Immunol

Abstract	Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents are degraded. The maintenance of cellular homeostasis is key in the survival and function of a variety of human cell populations. The interconnection between metabolism and autophagy is extensive, therefore it has a role in a variety of different cell functions. The disruption or dysfunction of autophagy in these cell types have been implicated in the development of a variety of inflammatory diseases including asthma. The role of autophagy in non-immune and immune cells both lead to the pathogenesis of lung inflammation. Autophagy in pulmonary non-immune cells leads to tissue remodeling which can develop into chronic asthma cases with long term effects. The role autophagy in the lymphoid and myeloid lineages in the pathology of asthma differ in their functions. Impaired autophagy in lymphoid populations have been shown, in general, to decrease inflammation in both asthma and inflammatory disease models. Many lymphoid cells rely on autophagy for effector function and maintained inflammation. In stark contrast, autophagy deficient antigen presenting cells have been shown to have an activated inflammasome. This is largely characterized by a TH17 response that is accompanied with a much worse prognosis including granulocyte mediated inflammation and steroid resistance. The cell specificity associated with changes in autophagic flux complicates its targeting for amelioration of asthmatic symptoms. Differing asthmatic phenotypes between TH2 and TH17 mediated disease may require different autophagic modulations. Therefore, treatments call for a more cell specific and personalized approach when looking at chronic asthma cases. Viral-induced lung inflammation, such as that caused by SARS-CoV-2, also may involve autophagic modulation leading to inflammation mediated by lung resident cells. In this review, we will be discussing the role of autophagy in non-immune cells, myeloid cells, and lymphoid cells for their implications into lung inflammation and asthma. Finally, we will discuss autophagy's role viral pathogenesis, immunometabolism, and asthma with insights into autophagic modulators for amelioration of lung inflammation.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #687353
Database	COVID19

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Article ; Online: "Advancing" Advance Care Planning to Veterans in the Veterans Health Administration.

Matthieu, Monica M / Ounpraseuth, Songthip T / Williams, J Silas / Hu, Bo / Adkins, David A / Taylor, Laura D / Oliver, Ciara M / Smith, Robin M / Painter, Jacob T / McCullough, Jane Ann / Garner, Kimberly K

Military medicine

2023 Volume 188, Issue 3-4, Page(s) 786–791

Abstract: Introduction: The completion rate of Advance Directive (ADs) in the Veterans Health Administration (VHA) is unknown. There is substantial literature on the need for effective Advance Care Planning (ACP) that leads to an AD to ensure that health care ... ...

Abstract	Introduction: The completion rate of Advance Directive (ADs) in the Veterans Health Administration (VHA) is unknown. There is substantial literature on the need for effective Advance Care Planning (ACP) that leads to an AD to ensure that health care preferences for patients are known. Advance Directive are essential to consider since ACP, which explains and plans Advance Directive, does not reach all individuals. Health inequities, such as those experienced in rural areas, continue to exist. While ACP may disproportionately affect rural-residing veterans and their providers, a VHA program was specifically designed to increase ACP engagement with rural veterans and to address several systemic barriers to ACP. Materials and methods: This descriptive analysis seeks to identify patient, provider, and geographic characteristics associated with higher rates of ACP participation in VHA. An observational examination of the profile of veterans and the types of ACP (e.g., individual or in groups) using administrative data for all beneficiaries receiving VHA health care services in federal fiscal year (FY) 2020 was conducted as part of a national program evaluation. The measures include patient-level data on demographics (e.g., race, ethnicity, gender), unique patient identifiers (e.g., name, social security number), geographic characteristics of patient's location (e.g., rurality defined as Rural-Urban Commuting Areas [RUCA]), VHA priority group; provider-level data (e.g., type of document definition, clinic stop codes, visit date used to verify Advance Care Planning via Group Visits [ACP-GV] attendance; data not shown), and electronic health record note titles that indicated the presence of ACP in VHA (e.g., "Advance Directive [AD] Discussion" note title, "ACP-GV CHAR 4 code"). Pearson's chi-square statistics were used for between-group comparisons based on a two-sided test with a significance level of 0.05. Results: The overall rate of AD discussions among unique VHA users in FY2020 was 5.2% (95% CI: 5.2%-5.2%) and for Advance Care Planning via Group Visits, which targets rural veterans using groups, it was 1.8% (95% CI: 1.8%-1.9%). Advance Directive discussions in VHA are more successful at reaching middle age (M = 64; SD = 16), African Americans, males, veterans living in urban areas, and veterans with a VA disability (Priority Group 1-4). Advance Care Planning delivered in groups is reaching slightly younger veterans under the age of 75 years (M = 62; SD = 15), African Americans, females, disabled veterans (e.g., Priority Group 1-4), and more veterans residing in rural communities compared to the national population of VHA users. Conclusion: Advance Directive discussion rates are low across VHA, yet intentional efforts with ACP via group visits are reaching veterans who are considered underserved owing to residing in rural areas. Advance Care Planning needs to be a well-informed clinical priority for VHA to engage with the entire veteran population and to support the completion of ADs.
MeSH term(s)	Male ; Middle Aged ; Female ; Humans ; Aged ; Veterans ; Veterans Health ; Advance Care Planning ; Advance Directives ; Surveys and Questionnaires
Language	English
Publishing date	2023-03-16
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	391061-1
ISSN	1930-613X ; 0026-4075
ISSN (online)	1930-613X
ISSN	0026-4075
DOI	10.1093/milmed/usac196
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Article ; Online: Cannabinoid receptor 2 engagement promotes group 2 innate lymphoid cell expansion and enhances airway hyperreactivity.

Hurrell, Benjamin P / Helou, Doumet Georges / Shafiei-Jahani, Pedram / Howard, Emily / Painter, Jacob D / Quach, Christine / Akbari, Omid

The Journal of allergy and clinical immunology

2021 Volume 149, Issue 5, Page(s) 1628–1642.e10

Abstract: Background: Cannabinoids modulate the activation of immune cells and physiologic processes in the lungs. Group 2 innate lymphoid cells (ILC2s) are central players in type 2 asthma, but how cannabinoids modulate ILC2 activation remains to be elucidated.!# ...

Abstract	Background: Cannabinoids modulate the activation of immune cells and physiologic processes in the lungs. Group 2 innate lymphoid cells (ILC2s) are central players in type 2 asthma, but how cannabinoids modulate ILC2 activation remains to be elucidated. Objective: Our goal was to investigate the effects of cannabinoids on ILC2s and their role in asthma. Methods: A combination of cannabinoid receptor (CB) Results: We provide evidence that CB Conclusion: Collectively, our results define CB
MeSH term(s)	Animals ; Asthma ; Cannabinoids ; Cell Proliferation ; Cytokines ; Humans ; Immunity, Innate ; Inflammation ; Interleukin-33 ; Lung ; Lymphocytes ; Mice ; Mice, Knockout ; Pneumonia ; Receptor, Cannabinoid, CB2 ; Receptors, Cannabinoid
Chemical Substances	Cannabinoids ; Cytokines ; Interleukin-33 ; Receptor, Cannabinoid, CB2 ; Receptors, Cannabinoid
Language	English
Publishing date	2021-10-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2021.09.037
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