A Lipopolysaccharide-Enriched Cow's Milk Allergy Microbiome Promotes a TLR4-Dependent Proinflammatory Intestinal Immune Response
In this study we selected a CMA-associated microbiota with increased abundance of Gram-negative bacteria for analysis of its proinflammatory potential. LPS is the major component of the outer membrane of Gram-negative bacteria. Colonization of mice with a global or conditional mutation of the LPS receptor TLR4 with this CMA microbiota induced expression of serum amyloid A1 (Saa1) and other Th17-, B cell-, and Th2-associated genes in the ileal epithelium in a TLR4-dependent manner. In agreement with the gene expression data, mice colonized with the CMA microbiota have expanded populations of Th17 and regulatory T cells and ...
Source: Journal of Immunology - January 3, 2024 Category: Allergy & Immunology Authors: Evelyn Campbell Lauren A Hesser Roberto Berni Canani Laura Carucci Lorella Paparo Robert T Patry Cathryn R Nagler Source Type: research
Rational Engineering of Islet Tolerance via Biomaterial-Mediated Immune Modulation
J Immunol. 2024 Jan 15;212(2):216-224. doi: 10.4049/jimmunol.2300527.ABSTRACTType 1 diabetes (T1D) onset is characterized by an autoimmune attack on β islet cells within the pancreas, preventing the insulin secretion required to maintain glucose homeostasis. Targeted modulation of key immunoregulatory cell populations is a promising strategy to restore tolerance to β cells. This strategy can be used to prevent T1D onset or reverse T1D with transplanted islets. To this end, drug delivery systems can be employed to transport immunomodulatory cargo to specific cell populations that inhibit autoreactive T cell-mediated destr...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Natalie Klug Jacqueline Burke Evan Scott Source Type: research
Materials-Based Approaches for Cancer Vaccination
J Immunol. 2024 Jan 15;212(2):179-187. doi: 10.4049/jimmunol.2300482.ABSTRACTTherapeutic cancer vaccines offer the promise of stimulating the immune system to specifically eradicate tumor cells and establish long-term memory to prevent tumor recurrence. However, despite showing benign safety profiles and the ability to generate Ag-specific cellular responses, cancer vaccines have been hampered by modest clinical efficacy. Lessons learned from these studies have led to the emergence of innovative materials-based strategies that aim to boost the clinical activity of cancer vaccines. In this Brief Review, we provide an overvi...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Miguel C Sobral David J Mooney Source Type: research
Engineering Strategies to Modulate the Gut Microbiome and Immune System
J Immunol. 2024 Jan 15;212(2):208-215. doi: 10.4049/jimmunol.2300480.ABSTRACTThe gut microbiota, predominantly residing in the colon, is a complex ecosystem with a pivotal role in the host immune system. Dysbiosis of the gut microbiota has been associated with various diseases, and there is an urgent need to develop new therapeutics that target the microbiome and restore immune functions. This Brief Review discusses emerging therapeutic strategies that focus on oral delivery systems for modulating the gut microbiome. These strategies include genetic engineering of probiotics, probiotic-biomaterial hybrids, dietary fibers, ...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Kai Han Jin Xu Fang Xie Julia Crowther James J Moon Source Type: research
Microengineered In Vitro Assays for Screening and Sorting Manufactured Therapeutic T Cells
J Immunol. 2024 Jan 15;212(2):199-207. doi: 10.4049/jimmunol.2300488.ABSTRACTAdoptively transferred T cells constitute a major class of current and emergent cellular immunotherapies for the treatment of disease, including but not limited to cancer. Although key advancements in molecular recognition, genetic engineering, and manufacturing have dramatically enhanced their translational potential, therapeutic potency remains limited by poor homing and infiltration of transferred cells within target host tissues. In vitro microengineered homing assays with precise control over micromechanical and biological cues can address th...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Abir K Muhuri Yunus Alapan Camila P Camargo Susan N Thomas Source Type: research
Engineering Anticytokine Antibodies for Immune Modulation
J Immunol. 2024 Jan 15;212(2):225-234. doi: 10.4049/jimmunol.2300467.ABSTRACTThe delicate balance of immune homeostasis is regulated by the interactions between cytokines and their cognate cell surface signaling receptors. There is intensive interest in harnessing cytokines as drugs for diseases such as cancer and autoimmune disorders. However, the multifarious and often contradictory activities of cytokines, coupled with their short serum half-lives, limit clinical performance and result in dangerous toxicities. There is thus growing emphasis on manipulating natural cytokines to enhance their selectivity, safety, and dura...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Jakub Tomala Shanelle D Cao Jamie B Spangler Source Type: research
Advancing Antibody Engineering through Synthetic Evolution and Machine Learning
J Immunol. 2024 Jan 15;212(2):235-243. doi: 10.4049/jimmunol.2300492.ABSTRACTAbs are versatile molecules with the potential to achieve exceptional binding to target Ags, while also possessing biophysical properties suitable for therapeutic drug development. Protein display and directed evolution systems have transformed synthetic Ab discovery, engineering, and optimization, vastly expanding the number of Ab clones able to be experimentally screened for binding. Moreover, the burgeoning integration of high-throughput screening, deep sequencing, and machine learning has further augmented in vitro Ab optimization, promising t...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Edward B Irvine Sai T Reddy Source Type: research
Immunoengineering a Future of Molecular, Material, and Cellular Therapeutics
J Immunol. 2024 Jan 15;212(2):167-168. doi: 10.4049/jimmunol.2300773.NO ABSTRACTPMID:38166250 | DOI:10.4049/jimmunol.2300773 (Source: Journal of Immunology)
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Jeffrey A Hubbell Source Type: research
Engineering Challenges and Opportunities in Autologous Cellular Cancer Immunotherapy
J Immunol. 2024 Jan 15;212(2):188-198. doi: 10.4049/jimmunol.2300642.ABSTRACTThe use of a patient's own immune or tumor cells, manipulated ex vivo, enables Ag- or patient-specific immunotherapy. Despite some clinical successes, there remain significant barriers to efficacy, broad patient population applicability, and safety. Immunotherapies that target specific tumor Ags, such as chimeric Ag receptor T cells and some dendritic cell vaccines, can mount robust immune responses against immunodominant Ags, but evolving tumor heterogeneity and antigenic downregulation can drive resistance. In contrast, whole tumor cell vaccines...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Colleen R Foley Sheridan L Swan Melody A Swartz Source Type: research
Modulating Antigen Availability in Lymphoid Organs to Shape the Humoral Immune Response to Vaccines
J Immunol. 2024 Jan 15;212(2):171-178. doi: 10.4049/jimmunol.2300500.ABSTRACTPrimary immune responses following vaccination are initiated in draining lymph nodes, where naive T and B cells encounter Ag and undergo coordinated steps of activation. For humoral immunity, the amount of Ag present over time, its localization to follicles and follicular dendritic cells, and the Ag's structural state all play important roles in determining the subsequent immune response. Recent studies have shown that multiple elements of vaccine design can impact Ag availability in lymphoid tissues, including the choice of adjuvant, physical for...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Aereas Aung Darrell J Irvine Source Type: research
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J Immunol. 2024 Jan 15;212(2):169. doi: 10.4049/jimmunol.2390023.NO ABSTRACTPMID:38166253 | DOI:10.4049/jimmunol.2390023 (Source: Journal of Immunology)
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Source Type: research
Rational Engineering of Islet Tolerance via Biomaterial-Mediated Immune Modulation
J Immunol. 2024 Jan 15;212(2):216-224. doi: 10.4049/jimmunol.2300527.ABSTRACTType 1 diabetes (T1D) onset is characterized by an autoimmune attack on β islet cells within the pancreas, preventing the insulin secretion required to maintain glucose homeostasis. Targeted modulation of key immunoregulatory cell populations is a promising strategy to restore tolerance to β cells. This strategy can be used to prevent T1D onset or reverse T1D with transplanted islets. To this end, drug delivery systems can be employed to transport immunomodulatory cargo to specific cell populations that inhibit autoreactive T cell-mediated destr...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Natalie Klug Jacqueline Burke Evan Scott Source Type: research
Materials-Based Approaches for Cancer Vaccination
J Immunol. 2024 Jan 15;212(2):179-187. doi: 10.4049/jimmunol.2300482.ABSTRACTTherapeutic cancer vaccines offer the promise of stimulating the immune system to specifically eradicate tumor cells and establish long-term memory to prevent tumor recurrence. However, despite showing benign safety profiles and the ability to generate Ag-specific cellular responses, cancer vaccines have been hampered by modest clinical efficacy. Lessons learned from these studies have led to the emergence of innovative materials-based strategies that aim to boost the clinical activity of cancer vaccines. In this Brief Review, we provide an overvi...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Miguel C Sobral David J Mooney Source Type: research
Engineering Strategies to Modulate the Gut Microbiome and Immune System
J Immunol. 2024 Jan 15;212(2):208-215. doi: 10.4049/jimmunol.2300480.ABSTRACTThe gut microbiota, predominantly residing in the colon, is a complex ecosystem with a pivotal role in the host immune system. Dysbiosis of the gut microbiota has been associated with various diseases, and there is an urgent need to develop new therapeutics that target the microbiome and restore immune functions. This Brief Review discusses emerging therapeutic strategies that focus on oral delivery systems for modulating the gut microbiome. These strategies include genetic engineering of probiotics, probiotic-biomaterial hybrids, dietary fibers, ...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Kai Han Jin Xu Fang Xie Julia Crowther James J Moon Source Type: research
Engineering Anticytokine Antibodies for Immune Modulation
J Immunol. 2024 Jan 15;212(2):225-234. doi: 10.4049/jimmunol.2300467.ABSTRACTThe delicate balance of immune homeostasis is regulated by the interactions between cytokines and their cognate cell surface signaling receptors. There is intensive interest in harnessing cytokines as drugs for diseases such as cancer and autoimmune disorders. However, the multifarious and often contradictory activities of cytokines, coupled with their short serum half-lives, limit clinical performance and result in dangerous toxicities. There is thus growing emphasis on manipulating natural cytokines to enhance their selectivity, safety, and dura...
Source: Journal of Immunology - January 2, 2024 Category: Allergy & Immunology Authors: Jakub Tomala Shanelle D Cao Jamie B Spangler Source Type: research
