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Article ; Online: The role of baseline 2-[

Albano, Domenico / Calabrò, Anna / Dondi, Francesco / Bagnasco, Samuele / Tucci, Alessandra / Bertagna, Francesco

2024 Volume 42, Issue 2, Page(s) e3266

Abstract: Diffuse Large B-Cell Lymphomas (DLCBL) and mucosa-associated lymphoid tissue (MALT) are the two most common primary gastric lymphomas (PGLs), but have strongly different features. DLBCL is more aggressive, is frequently diagnosed at an advanced stage and ...

Abstract	Diffuse Large B-Cell Lymphomas (DLCBL) and mucosa-associated lymphoid tissue (MALT) are the two most common primary gastric lymphomas (PGLs), but have strongly different features. DLBCL is more aggressive, is frequently diagnosed at an advanced stage and has a poorer prognosis. The aim of this retrospective study was to explore the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[
MeSH term(s)	Humans ; Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Lymphoma, B-Cell, Marginal Zone ; Radiomics ; Retrospective Studies ; Lymphoma, Non-Hodgkin ; Organothiophosphorus Compounds ; Stomach Neoplasms
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; VX (9A4381183B) ; Organothiophosphorus Compounds
Language	English
Publishing date	2024-03-05
Publishing country	England
Document type	Journal Article
ZDB-ID	604884-5
ISSN	1099-1069 ; 0278-0232
ISSN (online)	1099-1069
ISSN	0278-0232
DOI	10.1002/hon.3266
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Article ; Online: Innate and Adaptive Immunity to Transfused Allogeneic RBCs in Mice Requires MyD88.

Soldatenko, Arielle / Hoyt, Laura R / Xu, Lan / Calabro, Samuele / Lewis, Steven M / Gallman, Antonia E / Hudson, Krystalyn E / Stowell, Sean R / Luckey, Chance J / Zimring, James C / Liu, Dong / Santhanakrishnan, Manjula / Hendrickson, Jeanne E / Eisenbarth, Stephanie C

Journal of immunology (Baltimore, Md. : 1950)

2022 Volume 208, Issue 4, Page(s) 991–997

Abstract: RBC transfusion therapy is essential for the treatment of anemia. A serious complication of transfusion is the development of non-ABO alloantibodies to polymorphic RBC Ags; yet, mechanisms of alloantibody formation remain unclear. Storage of mouse RBCs ... ...

Abstract	RBC transfusion therapy is essential for the treatment of anemia. A serious complication of transfusion is the development of non-ABO alloantibodies to polymorphic RBC Ags; yet, mechanisms of alloantibody formation remain unclear. Storage of mouse RBCs before transfusion increases RBC immunogenicity through an unknown mechanism. We previously reported that sterile, stored mouse RBCs activate splenic dendritic cells (DCs), which are required for alloimmunization. Here we transfused mice with allogeneic RBCs to test whether stored RBCs activate pattern recognition receptors (PRRs) on recipient DCs to induce adaptive immunity. TLRs are a class of PRRs that regulate DC activation, which signal through two adapter molecules: MyD88 and TRIF. We show that the inflammatory cytokine response, DC activation and migration, and the subsequent alloantibody response to transfused RBCs require MyD88 but not TRIF, suggesting that a restricted set of PRRs are responsible for sensing RBCs and triggering alloimmunization.
MeSH term(s)	Adaptive Immunity ; Animals ; Biomarkers ; Erythrocyte Transfusion ; Erythrocytes/immunology ; Erythrocytes/metabolism ; Fluorescent Antibody Technique ; Humans ; Immunity, Innate ; Isoantibodies/immunology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Myeloid Differentiation Factor 88/genetics ; Myeloid Differentiation Factor 88/metabolism
Chemical Substances	Biomarkers ; Isoantibodies ; Myd88 protein, mouse ; Myeloid Differentiation Factor 88
Language	English
Publishing date	2022-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2100784
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Article ; Online: Coagulation Derangements in Patients With Refractory Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

Ruggeri, Laura / Franco, Annalisa / Alba, Ada Carla / Lembo, Rosalba / Frassoni, Samuele / Scandroglio, Anna Mara / Calabrò, Maria Grazia / Zangrillo, Alberto / Pappalardo, Federico

Journal of cardiothoracic and vascular anesthesia

2018 Volume 33, Issue 7, Page(s) 1877–1882

Abstract: Objective: Extracorporeal cardiopulmonary resuscitation (eCPR) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is gaining importance as a rescue therapy for refractory cardiac arrest. VA-ECMO, especially in the setting of eCPR, is ... ...

Abstract	Objective: Extracorporeal cardiopulmonary resuscitation (eCPR) with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is gaining importance as a rescue therapy for refractory cardiac arrest. VA-ECMO, especially in the setting of eCPR, is plagued by hemorrhagic and thromboembolic complications. The authors' aims were to describe the coagulation profile in refractory cardiac arrest and assess its prognostic role. Design: Single-center retrospective study. Setting: Cardiac surgical intensive care unit of a university hospital. Participants: One hundred eighty-eight patients treated with eCPR for intra-hospital and out-of-hospital refractory cardiac arrest, between 2008 and 2017. Interventions: The authors retrospectively analyzed data from the first blood sample drawn during cannulation for VA-ECMO to understand the association of coagulation parameters with survival to hospital discharge, number of blood components transfused, anticoagulation therapy, serum lactate levels, no-flow time, and low-flow time. Measurements and main results: Platelet count was 126 ± 79 × 10 Conclusion: Coagulation derangements are frequent in patients with refractory cardiac arrest and have important consequences for eCPR management for anticoagulant therapy and blood product transfusion. The presence of DIC diagnostic criteria should be considered among the prognostic factors in this population of patients.
MeSH term(s)	Adult ; Aged ; Blood Coagulation ; Cardiopulmonary Resuscitation ; Disseminated Intravascular Coagulation/drug therapy ; Extracorporeal Membrane Oxygenation ; Heart Arrest/therapy ; Humans ; Logistic Models ; Middle Aged ; Retrospective Studies
Language	English
Publishing date	2018-11-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	1067317-9
ISSN	1532-8422 ; 1053-0770
ISSN (online)	1532-8422
ISSN	1053-0770
DOI	10.1053/j.jvca.2018.11.014
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Zs.MO 31: Show issues

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Article ; Online: Combinations of Toll-like receptor 8 agonist TL8-506 activate human tumor-derived dendritic cells.

He, Mi / Soni, Bhavesh / Schwalie, Petra C / Hüsser, Tamara / Waltzinger, Caroline / De Silva, Duvini / Prinz, Ylva / Krümpelmann, Laura / Calabro, Samuele / Matos, Ines / Trumpfheller, Christine / Bacac, Marina / Umaña, Pablo / Levesque, Mitchell P / Dummer, Reinhard / van den Broek, Maries / Gasser, Stephan

Journal for immunotherapy of cancer

2022 Volume 10, Issue 6

Abstract: Background: Dendritic cells (DCs) are professional antigen presenting cells that initiate immune defense to pathogens and tumor cells. Human tumors contain only few DCs that mostly display a non-activated phenotype. Hence, activation of tumor-associated ...

Abstract	Background: Dendritic cells (DCs) are professional antigen presenting cells that initiate immune defense to pathogens and tumor cells. Human tumors contain only few DCs that mostly display a non-activated phenotype. Hence, activation of tumor-associated DCs may improve efficacy of cancer immunotherapies. Toll-like receptor (TLR) agonists and interferons are known to promote DC maturation. However, it is unclear if DCs in human tumors respond to activation signals and which stimuli induce the optimal activation of human tumor DCs. Methods: We first screened combinations of TLR agonists, a STING agonist and interferons (IFNs) for their ability to activate human conventional DCs (cDCs). Two combinations: TL8-506 (a TLR8 agonist)+IFN-γ and TL8-506+Poly(I:C) (a TLR3 agonist) were studied in more detail. cDC1s and cDC2s derived from cord blood stem cells, blood or patient tumor samples were stimulated with either TL8-506+IFN-γ or TL8-506+Poly(I:C). Different activation markers were analyzed by ELISA, flow cytometry, NanoString nCounter Technology or single-cell RNA-sequencing. T cell activation and migration assays were performed to assess functional consequences of cDC activation. Results: We show that TL8-506 synergized with IFN-γ or Poly(I:C) to induce high expression of different chemokines and cytokines including interleukin (IL)-12p70 in human cord blood and blood cDC subsets in a combination-specific manner. Importantly, both combinations induced the activation of cDC subsets in patient tumor samples ex vivo. The expression of immunostimulatory genes important for anticancer responses including Conclusions: Our data suggest that cord blood-derived and blood-derived cDCs are a good surrogate to study treatment responses in human tumor cDCs. While most cDCs in human tumors display a non-activated phenotype, TL8-506 combinations drive human tumor cDCs towards an immunostimulatory phenotype associated with Th1 responses on stimulation. Hence, TL8-506-based combinations may be promising candidates to initiate or boost antitumor responses in patients with cancer.
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; Cytokines/metabolism ; Dendritic Cells ; Humans ; Interferon-gamma/metabolism ; Interferon-gamma/pharmacology ; Interleukin-12/metabolism ; Neoplasms ; Poly I-C/metabolism ; Poly I-C/pharmacology ; Toll-Like Receptor 8
Chemical Substances	Adjuvants, Immunologic ; Cytokines ; Toll-Like Receptor 8 ; Interleukin-12 (187348-17-0) ; Interferon-gamma (82115-62-6) ; Poly I-C (O84C90HH2L)
Language	English
Publishing date	2022-04-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2021-004268
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Article ; Online: Dynamic expression of BCL6 in murine conventional dendritic cells during in vivo development and activation.

Zhang, Ting-ting / Liu, Dong / Calabro, Samuele / Eisenbarth, Stephanie C / Cattoretti, Giorgio / Haberman, Ann M

PloS one

2014 Volume 9, Issue 6, Page(s) e101208

Abstract: The transcriptional repressor BCL6 plays an essential role in the development of germinal center B cells and follicular helper T cells. However, much less is known about the expression and function of BCL6 in other cell types. Here we report that during ... ...

Abstract	The transcriptional repressor BCL6 plays an essential role in the development of germinal center B cells and follicular helper T cells. However, much less is known about the expression and function of BCL6 in other cell types. Here we report that during murine dendritic cell (DC) ontogeny in vivo, BCL6 is not expressed in bone marrow hematopoietic stem cells, common DC precursors and committed precursors of conventional DCs (pre-cDCs), but is elevated in peripheral pre-cDCs. BCL6 protein levels rise as pre-cDCs differentiate into cDCs in secondary lymphoid organs. Elevated protein levels of Bcl6 are observed in all cDC subsets, with CD8α+ cDCs displaying the greatest levels. Co-staining of Ki-67 revealed BCL6hi cDCs to be more proliferative than BCL6lo cDCs. After adjuvant inoculation, BCL6 levels are significantly reduced in the CD11cint MHC class IIhi CD86hi cDCs. Activation-induced BCL6 reduction correlated with reduced proliferation. A LPS injection study further confirmed that, in response to microbial stimuli, BCL6 levels are dynamically regulated during the maturation of CD11cint MHC class IIhi splenic cDCs. This reduction of BCL6 levels in cDCs does not occur after LPS injection in MyD88-/- TRIF-/- mice. Thus, regulation of Bcl6 protein levels is dynamic in murine cDCs during development, maturation and activation in vivo.
MeSH term(s)	Adaptor Proteins, Vesicular Transport/deficiency ; Adaptor Proteins, Vesicular Transport/metabolism ; Adjuvants, Immunologic/pharmacology ; Animals ; CD11c Antigen/metabolism ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Dendritic Cells/cytology ; Dendritic Cells/drug effects ; Dendritic Cells/metabolism ; Down-Regulation/drug effects ; Ki-67 Antigen/metabolism ; Lipopolysaccharides/pharmacology ; Lymphoid Tissue/drug effects ; Lymphoid Tissue/metabolism ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88/deficiency ; Myeloid Differentiation Factor 88/metabolism ; Proto-Oncogene Proteins c-bcl-6/metabolism ; Spleen/cytology
Chemical Substances	Adaptor Proteins, Vesicular Transport ; Adjuvants, Immunologic ; CD11c Antigen ; Ki-67 Antigen ; Lipopolysaccharides ; Myeloid Differentiation Factor 88 ; Proto-Oncogene Proteins c-bcl-6 ; TICAM-1 protein, mouse
Language	English
Publishing date	2014-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0101208
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Article ; Online: Effect of Levosimendan on Renal Outcome in Cardiac Surgery Patients With Chronic Kidney Disease and Perioperative Cardiovascular Dysfunction: A Substudy of a Multicenter Randomized Trial.

Journal of cardiothoracic and vascular anesthesia

2018 Volume 32, Issue 5, Page(s) 2152–2159

Abstract: Objective: Acute kidney injury (AKI) occurs frequently after cardiac surgery. Levosimendan might reduce the incidence of AKI in patients undergoing cardiac surgery. The authors investigated whether levosimendan administration could reduce AKI incidence ... ...

Abstract	Objective: Acute kidney injury (AKI) occurs frequently after cardiac surgery. Levosimendan might reduce the incidence of AKI in patients undergoing cardiac surgery. The authors investigated whether levosimendan administration could reduce AKI incidence in a high-risk cardiac surgical population. Design: Post hoc analysis of a multicenter randomized trial. Setting: Cardiac surgery operating rooms and intensive care units of 14 centers in 3 countries. Participants: The study comprised 90 patients who underwent mitral valve surgery with an estimated glomerular filtration rate <60 mL/min/1.73 m Interventions: Patients were assigned randomly to receive levosimendan (0.025-0.2 μg/kg/min) or placebo in addition to standard inotropic treatment. Measurements and main results: Forty-six patients were assigned to receive levosimendan and 44 to receive placebo. Postoperative AKI occurred in 14 (30%) patients in the levosimendan group versus 23 (52%) in the placebo group (absolute difference -21.8; 95% confidence interval -41.7 to -1.97; p = 0.035). The incidence of major complications also was lower (18 [39%]) in the levosimendan group versus that in the placebo group (29 [66%]) (absolute difference -26.8 [-46.7 to -6.90]; p = 0.011). A trend toward lower serum creatinine at intensive care unit discharge was observed in the levosimendan group (1.18 [0.99-1.49] mg/dL) versus that in the placebo group (1.39 [1.05-1.76] mg/dL) (95% confidence interval -0.23 [-0.49 to 0.01]; p = 0.07). Conclusions: Levosimendan may improve renal outcome in cardiac surgery patients with chronic kidney disease undergoing mitral valve surgery who develop perioperative myocardial dysfunction. Results of this exploratory analysis should be investigated in future properly designed randomized controlled trials.
MeSH term(s)	Acute Kidney Injury/epidemiology ; Acute Kidney Injury/etiology ; Acute Kidney Injury/prevention & control ; Aged ; Brazil/epidemiology ; Cardiac Surgical Procedures/adverse effects ; Cardiotonic Agents/administration & dosage ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Glomerular Filtration Rate/drug effects ; Heart Valve Diseases/complications ; Heart Valve Diseases/surgery ; Humans ; Incidence ; Italy/epidemiology ; Male ; Middle Aged ; Mitral Valve/surgery ; Perioperative Period ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology ; Postoperative Complications/prevention & control ; Renal Insufficiency, Chronic ; Russia/epidemiology ; Simendan/administration & dosage ; Treatment Outcome
Chemical Substances	Cardiotonic Agents ; Simendan (349552KRHK)
Language	English
Publishing date	2018-02-26
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	1067317-9
ISSN	1532-8422 ; 1053-0770
ISSN (online)	1532-8422
ISSN	1053-0770
DOI	10.1053/j.jvca.2018.02.039
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Zs.MO 31: Show issues

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Article ; Online: Differential Intrasplenic Migration of Dendritic Cell Subsets Tailors Adaptive Immunity.

Calabro, Samuele / Liu, Dong / Gallman, Antonia / Nascimento, Manuela Sales L / Yu, Zizi / Zhang, Ting-Ting / Chen, Pei / Zhang, Biyan / Xu, Lan / Gowthaman, Uthaman / Krishnaswamy, Jayendra Kumar / Haberman, Ann M / Williams, Adam / Eisenbarth, Stephanie C

Cell reports

2016 Volume 16, Issue 9, Page(s) 2472–2485

Abstract: Evidence suggests that distinct splenic dendritic cell (DC) subsets activate either CD4+ or CD8+ T cells in vivo. This bias has been partially ascribed to differential antigen presentation; however, all DC subsets can activate both T cell lineages in ... ...

Abstract	Evidence suggests that distinct splenic dendritic cell (DC) subsets activate either CD4+ or CD8+ T cells in vivo. This bias has been partially ascribed to differential antigen presentation; however, all DC subsets can activate both T cell lineages in vitro. Therefore, we tested whether the organization of DC and T cell subsets in the spleen dictated this preference. We discovered that CD4+ and CD8+ T cells segregated within splenic T cell zones prior to immunization. After intravenous immunization, the two major conventional DC populations, distinguished by 33D1 and XCR1 staining, migrated into separate regions of the T cell zone: 33D1+ DCs migrated into the CD4+ T cell area, whereas XCR1+ DCs migrated into the CD8+ T cell area. Thus, the post-immunization location of each DC subset correlated with the T cell lineage it preferentially primes. Preventing this co-localization selectively impaired either CD4+ or CD8+ T cell immunity to blood-borne antigens.
MeSH term(s)	Adaptive Immunity ; Animals ; Antigen Presentation ; Antigens/administration & dosage ; Biomarkers/metabolism ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; Cell Movement ; Dendritic Cells/classification ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Erythrocyte Transfusion ; Gene Expression ; Immunization ; Immunophenotyping ; Isoantibodies/biosynthesis ; Lipopolysaccharides/administration & dosage ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin/administration & dosage ; Receptors, Chemokine/genetics ; Receptors, Chemokine/immunology ; Spleen/cytology ; Spleen/immunology
Chemical Substances	Antigens ; Biomarkers ; Isoantibodies ; Lipopolysaccharides ; Receptors, Chemokine ; XC chemokine receptor 1, mouse ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2016-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2016.07.076
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Article ; Online: Dynamic expression of BCL6 in murine conventional dendritic cells during in vivo development and activation.

Ting-ting Zhang / Dong Liu / Samuele Calabro / Stephanie C Eisenbarth / Giorgio Cattoretti / Ann M Haberman

PLoS ONE, Vol 9, Iss 6, p e

2014 Volume 101208

Abstract	The transcriptional repressor BCL6 plays an essential role in the development of germinal center B cells and follicular helper T cells. However, much less is known about the expression and function of BCL6 in other cell types. Here we report that during murine dendritic cell (DC) ontogeny in vivo, BCL6 is not expressed in bone marrow hematopoietic stem cells, common DC precursors and committed precursors of conventional DCs (pre-cDCs), but is elevated in peripheral pre-cDCs. BCL6 protein levels rise as pre-cDCs differentiate into cDCs in secondary lymphoid organs. Elevated protein levels of Bcl6 are observed in all cDC subsets, with CD8α+ cDCs displaying the greatest levels. Co-staining of Ki-67 revealed BCL6hi cDCs to be more proliferative than BCL6lo cDCs. After adjuvant inoculation, BCL6 levels are significantly reduced in the CD11cint MHC class IIhi CD86hi cDCs. Activation-induced BCL6 reduction correlated with reduced proliferation. A LPS injection study further confirmed that, in response to microbial stimuli, BCL6 levels are dynamically regulated during the maturation of CD11cint MHC class IIhi splenic cDCs. This reduction of BCL6 levels in cDCs does not occur after LPS injection in MyD88-/- TRIF-/- mice. Thus, regulation of Bcl6 protein levels is dynamic in murine cDCs during development, maturation and activation in vivo.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: The Nlrp3 Inflammasome Does Not Regulate Alloimmunization to Transfused Red Blood Cells in Mice.

Gibb, David R / Calabro, Samuele / Liu, Dong / Tormey, Christopher A / Spitalnik, Steven L / Zimring, James C / Hendrickson, Jeanne E / Hod, Eldad A / Eisenbarth, Stephanie C

EBioMedicine

2016 Volume 9, Page(s) 77–86

Abstract: Red blood cell (RBC) transfusions are essential for patients with hematological disorders and bone marrow failure syndromes. Despite ABO matching, RBC transfusions can lead to production of alloantibodies against "minor" blood group antigens. Non-ABO ... ...

Abstract	Red blood cell (RBC) transfusions are essential for patients with hematological disorders and bone marrow failure syndromes. Despite ABO matching, RBC transfusions can lead to production of alloantibodies against "minor" blood group antigens. Non-ABO alloimmunization is a leading cause of transfusion-associated mortality in the U.S. Despite its clinical importance, little is known about the immunological factors that promote alloimmunization. Prior studies indicate that inflammatory conditions place patients at higher risk for alloimmunization. Additionally, co-exposure to pro-inflammatory pathogen associated molecular patterns (PAMPs) promotes alloimmunization in animal models, suggesting that RBC alloimmunization depends on innate immune cell activation. However, the specific innate immune stimuli and sensors that induce a T cell-dependent alloantibody response to transfused RBCs have not been identified. The NLRP3 inflammasome senses chemically diverse PAMPs and damage associated molecular patterns (DAMPs), including extracellular ATP and iron-containing heme. We hypothesized that activation of the NLRP3 inflammasome by endogenous DAMPs from RBCs promotes the alloimmune response to a sterile RBC transfusion. Using genetically modified mice lacking either NLRP3 or multiple downstream inflammasome response elements, we ruled out a role for the NLRP3 inflammasome or any Caspase-1 or -11 dependent inflammasome in regulating RBC alloantibody production to a model antigen.
MeSH term(s)	Animals ; Blood Group Antigens/immunology ; Cytokines/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Erythrocyte Transfusion/adverse effects ; Erythrocytes/immunology ; Erythrocytes/metabolism ; Immunomodulation ; Immunophenotyping ; Inflammasomes/metabolism ; Inflammation/immunology ; Inflammation/metabolism ; Isoantibodies/immunology ; Isoantigens/immunology ; Mice ; Mice, Knockout ; Models, Animal ; Models, Biological ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Phenotype
Chemical Substances	Blood Group Antigens ; Cytokines ; Inflammasomes ; Isoantibodies ; Isoantigens ; NLR Family, Pyrin Domain-Containing 3 Protein
Language	English
Publishing date	2016-06-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2016.06.008
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Article ; Online: The Nlrp3 Inflammasome Does Not Regulate Alloimmunization to Transfused Red Blood Cells in Mice

David R. Gibb / Samuele Calabro / Dong Liu / Christopher A. Tormey / Steven L. Spitalnik / James C. Zimring / Jeanne E. Hendrickson / Eldad A. Hod / Stephanie C. Eisenbarth

EBioMedicine, Vol 9, Iss C, Pp 77-

2016 Volume 86

Abstract	Red blood cell (RBC) transfusions are essential for patients with hematological disorders and bone marrow failure syndromes. Despite ABO matching, RBC transfusions can lead to production of alloantibodies against “minor” blood group antigens. Non-ABO alloimmunization is a leading cause of transfusion-associated mortality in the U.S. Despite its clinical importance, little is known about the immunological factors that promote alloimmunization. Prior studies indicate that inflammatory conditions place patients at higher risk for alloimmunization. Additionally, co-exposure to pro-inflammatory pathogen associated molecular patterns (PAMPs) promotes alloimmunization in animal models, suggesting that RBC alloimmunization depends on innate immune cell activation. However, the specific innate immune stimuli and sensors that induce a T cell-dependent alloantibody response to transfused RBCs have not been identified. The NLRP3 inflammasome senses chemically diverse PAMPs and damage associated molecular patterns (DAMPs), including extracellular ATP and iron-containing heme. We hypothesized that activation of the NLRP3 inflammasome by endogenous DAMPs from RBCs promotes the alloimmune response to a sterile RBC transfusion. Using genetically modified mice lacking either NLRP3 or multiple downstream inflammasome response elements, we ruled out a role for the NLRP3 inflammasome or any Caspase-1 or -11 dependent inflammasome in regulating RBC alloantibody production to a model antigen.
Keywords	NLRP3 ; Inflammasome ; Alloimmunization ; Conventional dendritic cells (cDCs) ; Red blood cell (RBC) storage ; Medicine ; R
Subject code	616
Language	English
Publishing date	2016-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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