The Implant-Induced Foreign Body Response Is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins
J Immunol. 2023 Dec 27:ji2300688. doi: 10.4049/jimmunol.2300688. Online ahead of print.ABSTRACTImplanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant cells (FBGCs), accompanied by inflammatory cytokines, matrix deposition, and eventually deleterious fibrotic implant encapsulation. Despite efforts to impr...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Mallika Ghosh Fraser McGurk Rachael Norris Andy Dong Sreenidhi Nair Evan Jellison Patrick Murphy Rajkumar Verma Linda H Shapiro Source Type: research
Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs
In this study, we describe 6-(4-phenylpiperazin-1-yl)pyridine-3-carboximidamide (A1) as a selective, competitive inhibitor of C1s. A1 was identified through a virtual screen for small molecules that interact with the C1s substrate recognition site. Subsequent functional studies revealed that A1 dose-dependently inhibits CP activation by heparin-induced immune complexes, CP-driven lysis of Ab-sensitized sheep erythrocytes, CP activation in a pathway-specific ELISA, and cleavage of C2 by C1s. Biochemical experiments demonstrated that A1 binds directly to C1s with a Kd of ∼9.8 μM and competitively inhibits its activity wit...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Xin Xu Timothy J Herdendorf Huiquan Duan Denise L Rohlik Sourav Roy Hinman Zhou Haya Alkhateeb Sanjay Khandelwal Qilong Zhou Ping Li Gowthami M Arepally John K Walker Brandon L Garcia Brian V Geisbrecht Source Type: research
Defining Parameters That Modulate Susceptibility and Protection to Respiratory Murine Coronavirus MHV1 Infection
J Immunol. 2023 Dec 27:ji2300434. doi: 10.4049/jimmunol.2300434. Online ahead of print.ABSTRACTPatients infected with SARS-CoV-2 experience variable disease susceptibility, and patients with comorbidities such as sepsis are often hospitalized for COVID-19 complications. However, the extent to which initial infectious inoculum dose determines disease outcomes and whether this can be used for immunological priming in a genetically susceptible host has not been completely defined. We used an established SARS-like murine model in which responses to primary and/or secondary challenges with murine hepatitis virus type 1 (MHV-1) ...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Elvia E Silva Steven J Moioffer Mariah Hassert Roger R Berton Matthew G Smith Stephanie van de Wall David K Meyerholz Thomas S Griffith John T Harty Vladimir P Badovinac Source Type: research
Cross-Reactivity of Antibodies to Rituximab with Other Therapeutic Anti-CD20 Antibodies
In this study, we investigated the potential cross-reactivity of (human) anti-rituximab Abs to three other anti-CD20 mAbs: ofatumumab, obinutuzumab, and ocrelizumab. In 25 cases of anti-rituximab Abs, cross-reactivity was examined using both direct binding assays and inhibition immunoassays. Although no cross-reactivity was observed to ofatumumab or obinutuzumab, 8 of 25 samples also showed reactivity toward ocrelizumab in at least one of the two assays. Furthermore, in three cases of anti-ocrelizumab Abs, cross-reactivity to rituximab was observed in an inhibition immunoassay, albeit not in a direct binding assay. Our res...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Theo Rispens Taco W Kuijpers Joep Killestein Zo é L E van Kempen Karien Bloem Source Type: research
Effector-Phase IL-2 Signals Drive Th1 Effector and Memory Responses Dependently and Independently of TCF-1
In this study, we test whether TCR-dependent IL-2 links the TCR to CD4+ T cell differentiation. We employ a mixture of anti-IL-2 Abs to neutralize IL-2 throughout the primary CD4+ T cell response to lymphocytic choriomeningitis virus infection in mice or only after the establishment of lineage-committed effector cells (day 3 postinfection). We report that IL-2 signals drive the formation of Th1 precursor cells in the early stages of the immune response and sustain Th1 responses during its later stages (after day 3). Effector-stage IL-2 also shapes the composition and function of resulting CD4+ memory T cells. Although IL-2...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Krystal R Charley Andrew G Ramstead Joseph G Matous Yohichi Kumaki Linda M Sircy J Scott Hale Matthew A Williams Source Type: research
IFN- β Pretreatment Alleviates Allogeneic Renal Tubular Epithelial Cell-Induced NK Cell Responses via the IRF7/HLA-E/NKG2A Axis
In conclusion, IFN-β pretreatment could activate HLA-E and PD-L1 transcription through the JAK/STAT/IRF7 pathway and then could protect renal tubular epithelial cells from allogeneic immune attack mediated by NK cells.PMID:38149913 | DOI:10.4049/jimmunol.2200941 (Source: Journal of Immunology)
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Xing Zhang Junni Wang Mowang Wang Mengbao Du Jianghua Chen Limengmeng Wang Jianyong Wu Source Type: research
Inherently Reduced Expression of ASC Restricts Caspase-1 Processing in Hepatocytes and Promotes Plasmodium Infection
J Immunol. 2023 Dec 27:ji2300440. doi: 10.4049/jimmunol.2300440. Online ahead of print.ABSTRACTInflammasome-mediated caspase-1 activation facilitates innate immune control of Plasmodium in the liver, thereby limiting the incidence and severity of clinical malaria. However, caspase-1 processing occurs incompletely in both mouse and human hepatocytes and precludes the generation of mature IL-1β or IL-18, unlike in other cells. Why this is so or how it impacts Plasmodium control in the liver has remained unknown. We show that an inherently reduced expression of the inflammasome adaptor molecule apoptosis-associated specklike...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Camila Marques-da-Silva Clyde Schmidt-Silva Rodrigo P Baptista Samarchith P Kurup Source Type: research
The Implant-Induced Foreign Body Response Is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins
J Immunol. 2023 Dec 27:ji2300688. doi: 10.4049/jimmunol.2300688. Online ahead of print.ABSTRACTImplanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant cells (FBGCs), accompanied by inflammatory cytokines, matrix deposition, and eventually deleterious fibrotic implant encapsulation. Despite efforts to impr...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Mallika Ghosh Fraser McGurk Rachael Norris Andy Dong Sreenidhi Nair Evan Jellison Patrick Murphy Rajkumar Verma Linda H Shapiro Source Type: research
Inhibition of the C1s Protease and the Classical Complement Pathway by 6-(4-Phenylpiperazin-1-yl)Pyridine-3-Carboximidamide and Chemical Analogs
In this study, we describe 6-(4-phenylpiperazin-1-yl)pyridine-3-carboximidamide (A1) as a selective, competitive inhibitor of C1s. A1 was identified through a virtual screen for small molecules that interact with the C1s substrate recognition site. Subsequent functional studies revealed that A1 dose-dependently inhibits CP activation by heparin-induced immune complexes, CP-driven lysis of Ab-sensitized sheep erythrocytes, CP activation in a pathway-specific ELISA, and cleavage of C2 by C1s. Biochemical experiments demonstrated that A1 binds directly to C1s with a Kd of ∼9.8 μM and competitively inhibits its activity wit...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Xin Xu Timothy J Herdendorf Huiquan Duan Denise L Rohlik Sourav Roy Hinman Zhou Haya Alkhateeb Sanjay Khandelwal Qilong Zhou Ping Li Gowthami M Arepally John K Walker Brandon L Garcia Brian V Geisbrecht Source Type: research
Defining Parameters That Modulate Susceptibility and Protection to Respiratory Murine Coronavirus MHV1 Infection
J Immunol. 2023 Dec 27:ji2300434. doi: 10.4049/jimmunol.2300434. Online ahead of print.ABSTRACTPatients infected with SARS-CoV-2 experience variable disease susceptibility, and patients with comorbidities such as sepsis are often hospitalized for COVID-19 complications. However, the extent to which initial infectious inoculum dose determines disease outcomes and whether this can be used for immunological priming in a genetically susceptible host has not been completely defined. We used an established SARS-like murine model in which responses to primary and/or secondary challenges with murine hepatitis virus type 1 (MHV-1) ...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Elvia E Silva Steven J Moioffer Mariah Hassert Roger R Berton Matthew G Smith Stephanie van de Wall David K Meyerholz Thomas S Griffith John T Harty Vladimir P Badovinac Source Type: research
Cross-Reactivity of Antibodies to Rituximab with Other Therapeutic Anti-CD20 Antibodies
In this study, we investigated the potential cross-reactivity of (human) anti-rituximab Abs to three other anti-CD20 mAbs: ofatumumab, obinutuzumab, and ocrelizumab. In 25 cases of anti-rituximab Abs, cross-reactivity was examined using both direct binding assays and inhibition immunoassays. Although no cross-reactivity was observed to ofatumumab or obinutuzumab, 8 of 25 samples also showed reactivity toward ocrelizumab in at least one of the two assays. Furthermore, in three cases of anti-ocrelizumab Abs, cross-reactivity to rituximab was observed in an inhibition immunoassay, albeit not in a direct binding assay. Our res...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Theo Rispens Taco W Kuijpers Joep Killestein Zo é L E van Kempen Karien Bloem Source Type: research
Effector-Phase IL-2 Signals Drive Th1 Effector and Memory Responses Dependently and Independently of TCF-1
In this study, we test whether TCR-dependent IL-2 links the TCR to CD4+ T cell differentiation. We employ a mixture of anti-IL-2 Abs to neutralize IL-2 throughout the primary CD4+ T cell response to lymphocytic choriomeningitis virus infection in mice or only after the establishment of lineage-committed effector cells (day 3 postinfection). We report that IL-2 signals drive the formation of Th1 precursor cells in the early stages of the immune response and sustain Th1 responses during its later stages (after day 3). Effector-stage IL-2 also shapes the composition and function of resulting CD4+ memory T cells. Although IL-2...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Krystal R Charley Andrew G Ramstead Joseph G Matous Yohichi Kumaki Linda M Sircy J Scott Hale Matthew A Williams Source Type: research
IFN- β Pretreatment Alleviates Allogeneic Renal Tubular Epithelial Cell-Induced NK Cell Responses via the IRF7/HLA-E/NKG2A Axis
In conclusion, IFN-β pretreatment could activate HLA-E and PD-L1 transcription through the JAK/STAT/IRF7 pathway and then could protect renal tubular epithelial cells from allogeneic immune attack mediated by NK cells.PMID:38149913 | DOI:10.4049/jimmunol.2200941 (Source: Journal of Immunology)
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Xing Zhang Junni Wang Mowang Wang Mengbao Du Jianghua Chen Limengmeng Wang Jianyong Wu Source Type: research
Inherently Reduced Expression of ASC Restricts Caspase-1 Processing in Hepatocytes and Promotes Plasmodium Infection
J Immunol. 2023 Dec 27:ji2300440. doi: 10.4049/jimmunol.2300440. Online ahead of print.ABSTRACTInflammasome-mediated caspase-1 activation facilitates innate immune control of Plasmodium in the liver, thereby limiting the incidence and severity of clinical malaria. However, caspase-1 processing occurs incompletely in both mouse and human hepatocytes and precludes the generation of mature IL-1β or IL-18, unlike in other cells. Why this is so or how it impacts Plasmodium control in the liver has remained unknown. We show that an inherently reduced expression of the inflammasome adaptor molecule apoptosis-associated specklike...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Camila Marques-da-Silva Clyde Schmidt-Silva Rodrigo P Baptista Samarchith P Kurup Source Type: research
The Implant-Induced Foreign Body Response Is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins
J Immunol. 2023 Dec 27:ji2300688. doi: 10.4049/jimmunol.2300688. Online ahead of print.ABSTRACTImplanted medical devices, from artificial heart valves and arthroscopic joints to implantable sensors, often induce a foreign body response (FBR), a form of chronic inflammation resulting from the inflammatory reaction to a persistent foreign stimulus. The FBR is characterized by a subset of multinucleated giant cells (MGCs) formed by macrophage fusion, the foreign body giant cells (FBGCs), accompanied by inflammatory cytokines, matrix deposition, and eventually deleterious fibrotic implant encapsulation. Despite efforts to impr...
Source: Journal of Immunology - December 27, 2023 Category: Allergy & Immunology Authors: Mallika Ghosh Fraser McGurk Rachael Norris Andy Dong Sreenidhi Nair Evan Jellison Patrick Murphy Rajkumar Verma Linda H Shapiro Source Type: research
