Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model
J Immunol. 2024 Apr 24:ji2300495. doi: 10.4049/jimmunol.2300495. Online ahead of print.ABSTRACTThe thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, Ags. B cells also reside and develop in the thymus, although their functions are less clear. During "thymic involution," a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ∼1% of human neonatal thymocytes but up to ∼10% in adults. All jawed vertebrates possess a thymus, and we and others...
Source: Journal of Immunology - April 24, 2024 Category: Allergy & Immunology Authors: Ameera Hasan Jose J Macias Brash é Wood Megan Malone-Perez Gilseung Park Clay A Foster J Kimble Frazer Source Type: research

Glycan-Reactive Innate-like B Cells and Developmental Checkpoints
J Immunol. 2024 Apr 22:ji2300587. doi: 10.4049/jimmunol.2300587. Online ahead of print.ABSTRACTUsing an Ig H chain conferring specificity for N-acetyl-d-glucosamine (GlcNAc), we developed transgenic (VHHGAC39 TG) mice to study the role of self-antigens in GlcNAc-reactive B-1 B cell development. In VHHGAC39 TG mice, GlcNAc-reactive B-1 B cell development during ontogeny and in adult bone marrow was normal. However, adult TG mice exhibited a block at transitional-2 immature B cell stages, resulting in impaired allelic exclusion and accumulation of a B cell subset coexpressing endogenous Ig gene rearrangements. Similarly, VHH...
Source: Journal of Immunology - April 22, 2024 Category: Allergy & Immunology Authors: J Stewart New Brian L P Dizon John F Kearney R Glenn King Source Type: research

Separating the Wheat from the Chaff among HLA-DQ Eplets
J Immunol. 2024 Apr 22:ji2400030. doi: 10.4049/jimmunol.2400030. Online ahead of print.ABSTRACTIn transplantation, anti-HLA Abs, especially targeting the DQ locus, are well-known to lead to rejection. These Abs identified by Luminex single Ag assays recognize polymorphic amino acids on HLA, named eplets. The HLA Eplet Registry included 83 DQ eplets, mainly deduced from amino acid sequence alignments, among which 66 have not been experimentally verified. Because eplet mismatch load may improve organ allocation and transplant outcomes, it is imperative to confirm the genuine reactivity of eplets to validate this approach. Ou...
Source: Journal of Immunology - April 22, 2024 Category: Allergy & Immunology Authors: Magali Devriese Fran çois A Lemonnier Julien Lion Caroline Sayegh Emma Fleury Catherine Shofstall Lisa Giraldo Quentin Fiachetti C édric Usureau Hiroko Miyadera Olivier Toutirais Nuala Mooney Dave Lowe Jean-Luc Taupin Source Type: research

Single-Cell Analysis Uncovers Striking Cellular Heterogeneity of Lung-Infiltrating Regulatory T Cells during Eosinophilic versus Neutrophilic Allergic Airway Inflammation
J Immunol. 2024 Apr 22:ji2300646. doi: 10.4049/jimmunol.2300646. Online ahead of print.ABSTRACTAllergic airway inflammation results from uncontrolled immune responses to environmental Ags. Although it is well established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types such as eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the mechanisms responsible for such pathogenesis remain elusive. Foxp3+ regulatory T cells (Tregs) are essential immune regulators during chronic inflammation, including allergic airway inflammation. Emerging evidence su...
Source: Journal of Immunology - April 22, 2024 Category: Allergy & Immunology Authors: Supinya Iamsawat Rongzhen Yu Sohee Kim Nina Dvorina Kevin Qiu Jaehyuk Choi William M Baldwin Booki Min Source Type: research

Glycan-Reactive Innate-like B Cells and Developmental Checkpoints
J Immunol. 2024 Apr 22:ji2300587. doi: 10.4049/jimmunol.2300587. Online ahead of print.ABSTRACTUsing an Ig H chain conferring specificity for N-acetyl-d-glucosamine (GlcNAc), we developed transgenic (VHHGAC39 TG) mice to study the role of self-antigens in GlcNAc-reactive B-1 B cell development. In VHHGAC39 TG mice, GlcNAc-reactive B-1 B cell development during ontogeny and in adult bone marrow was normal. However, adult TG mice exhibited a block at transitional-2 immature B cell stages, resulting in impaired allelic exclusion and accumulation of a B cell subset coexpressing endogenous Ig gene rearrangements. Similarly, VHH...
Source: Journal of Immunology - April 22, 2024 Category: Allergy & Immunology Authors: J Stewart New Brian L P Dizon John F Kearney R Glenn King Source Type: research

Separating the Wheat from the Chaff among HLA-DQ Eplets
J Immunol. 2024 Apr 22:ji2400030. doi: 10.4049/jimmunol.2400030. Online ahead of print.ABSTRACTIn transplantation, anti-HLA Abs, especially targeting the DQ locus, are well-known to lead to rejection. These Abs identified by Luminex single Ag assays recognize polymorphic amino acids on HLA, named eplets. The HLA Eplet Registry included 83 DQ eplets, mainly deduced from amino acid sequence alignments, among which 66 have not been experimentally verified. Because eplet mismatch load may improve organ allocation and transplant outcomes, it is imperative to confirm the genuine reactivity of eplets to validate this approach. Ou...
Source: Journal of Immunology - April 22, 2024 Category: Allergy & Immunology Authors: Magali Devriese Fran çois A Lemonnier Julien Lion Caroline Sayegh Emma Fleury Catherine Shofstall Lisa Giraldo Quentin Fiachetti C édric Usureau Hiroko Miyadera Olivier Toutirais Nuala Mooney Dave Lowe Jean-Luc Taupin Source Type: research

Single-Cell Analysis Uncovers Striking Cellular Heterogeneity of Lung-Infiltrating Regulatory T Cells during Eosinophilic versus Neutrophilic Allergic Airway Inflammation
J Immunol. 2024 Apr 22:ji2300646. doi: 10.4049/jimmunol.2300646. Online ahead of print.ABSTRACTAllergic airway inflammation results from uncontrolled immune responses to environmental Ags. Although it is well established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types such as eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the mechanisms responsible for such pathogenesis remain elusive. Foxp3+ regulatory T cells (Tregs) are essential immune regulators during chronic inflammation, including allergic airway inflammation. Emerging evidence su...
Source: Journal of Immunology - April 22, 2024 Category: Allergy & Immunology Authors: Supinya Iamsawat Rongzhen Yu Sohee Kim Nina Dvorina Kevin Qiu Jaehyuk Choi William M Baldwin Booki Min Source Type: research

The NLRP3 Inflammasome Is a Major Cause of Acute Renal Failure Induced by Polypeptide Antibiotics
J Immunol. 2024 Apr 19:ji2300193. doi: 10.4049/jimmunol.2300193. Online ahead of print.ABSTRACTDrug-induced acute renal failure (ARF) is a public health concern that hinders optimal drug therapy. However, pathological mechanisms of drug-induced ARF remain to be elucidated. Here, we show that a pathological process of drug-induced ARF is mediated by proinflammatory cross-talk between kidney tubular cells and macrophages. Both polymyxin B and colistin, polypeptide antibiotics, frequently cause ARF, stimulated the ERK and NF-κB pathways in kidney tubular cells, and thereby upregulated M-CSF and MCP-1, leading to infiltration...
Source: Journal of Immunology - April 19, 2024 Category: Allergy & Immunology Authors: Tomohiro Kagi Aya Inoue Takuya Noguchi Wakana Suzuki Saya Takano Kohei Otani Rio Naganuma Yuto Sekiguchi Yusuke Hirata Sawako Shindo Gi-Wook Hwang Atsushi Matsuzawa Source Type: research

Sialyl Lewis X Defines an Activated and Functional Regulatory T Cell Subpopulation in Mice
In this study, we report that sLex defines the activated and functional subset of murine Tregs. The contact hypersensitivity model showed that murine Tregs strongly express sLex upon activation, accompanied by functional Treg marker elevation, such as Foxp3, CD25, CD103, CD39, and granzyme B. RNA sequencing analysis revealed sLex-positive (sLex+) Tregs expressed genes involved in Treg function at a higher level than sLex-negative (sLex-) Tregs. Using an in vitro suppression assay, we found that sLex+ Tregs could more efficiently suppress naive CD4+ T cell proliferation than sLex- Tregs. In the murine contact hypersensitivi...
Source: Journal of Immunology - April 19, 2024 Category: Allergy & Immunology Authors: Kanae Ohishi Asaki Ishikura Shogo Nishida Hirohito Abo Hiroko Nakatsukasa Hiroto Kawashima Source Type: research

Complete Genomic Assembly of Mauritian Cynomolgus Macaque Killer Ig-like Receptor and Natural Killer Group 2 Haplotypes
In this study, we employ advanced long-read sequencing techniques to completely assemble eight KIR and seven NKG2 genomic haplotypes, providing an extensive insight into the structural and allelic diversity of these immunoregulatory gene clusters. Leveraging these genomic resources, we prototype a strategy for genotyping KIR and NKG2 using short-read, whole-exome capture data, illustrating the potential for cost-effective multilocus genotyping at colony scale. These results mark a significant enhancement for biomedical research in MCMs and underscore the feasibility of broad-scale genetic investigations.PMID:38639635 | DOI...
Source: Journal of Immunology - April 19, 2024 Category: Allergy & Immunology Authors: Trent M Prall Julie A Karl Joshua M Varghese David A Baker Nicholas R Minor Muthuswamy Raveendran R Alan Harris Jeffery Rogers Roger W Wiseman David H O'Connor Source Type: research

Enterovirus 71 Activates Plasmacytoid Dendritic Cell-Dependent PSGL-1 Binding Independent of Productive Infection
J Immunol. 2024 Apr 17:ji2300407. doi: 10.4049/jimmunol.2300407. Online ahead of print.ABSTRACTEnterovirus 71 (EV71) is a significant causative agent of hand, foot, and mouth disease, with potential serious neurologic complications or fatal outcomes. The lack of effective treatments for EV71 infection is attributed to its elusive pathogenicity. Our study reveals that human plasmacytoid dendritic cells (pDCs), the main type I IFN-producing cells, selectively express scavenger receptor class B, member 2 (SCARB2) and P-selectin glycoprotein ligand 1 (PSGL-1), crucial cellular receptors for EV71. Some strains of EV71 can repli...
Source: Journal of Immunology - April 17, 2024 Category: Allergy & Immunology Authors: Xuyuan Zhang Zhao Yin Jialong Zhang Hao Guo Jingyun Li Xiaohua Nie Shouli Wang Liguo Zhang Source Type: research

TLR Engagement Induces an Alternate Pathway for BCR Signaling that Results in PKC δ Phosphorylation
J Immunol. 2024 Apr 17:ji2300784. doi: 10.4049/jimmunol.2300784. Online ahead of print.ABSTRACTRecently, we reported that preexposure of B cells to IL-4 induced an alternate, signalosome-independent BCR signaling pathway leading to protein kinase C (PKC)δ phosphorylation (pTyr311), which occurs in the membrane compartment. This is considered to represent a form of receptor crosstalk and signal integration. Unlike the classical BCR signaling pathway, Lyn kinase is indispensable for BCR-induced downstream events in the alternate pathway. Our previous report that alternate BCR signaling leading to ERK phosphorylation is trig...
Source: Journal of Immunology - April 17, 2024 Category: Allergy & Immunology Authors: Naeem Khan Yongmei Hu Clifford A Lowell Thomas L Rothstein Source Type: research

Chickens with a Truncated Light Chain Transgene Express Single-Domain H Chain-Only Antibodies
J Immunol. 2024 Apr 17:ji2300617. doi: 10.4049/jimmunol.2300617. Online ahead of print.ABSTRACTH chain-only Igs are naturally produced in camelids and sharks. Because these Abs lack the L chain, the Ag-binding domain is half the size of a traditional Ab, allowing this type of Ig to bind to targets in novel ways. Consequently, the H chain-only single-domain Ab (sdAb) structure has the potential to increase the repertoire and functional range of an active humoral immune system. The majority of vertebrates use the standard heterodimeric (both H and L chains) structure and do not produce sdAb format Igs. To investigate if othe...
Source: Journal of Immunology - April 17, 2024 Category: Allergy & Immunology Authors: Philip A Leighton Kathryn Ching Kevin Reynolds Christine N Vuong Baisen Zeng Yulei Zhang Abheepsa Gupta Jacqueline Morales Gerry Sann Rivera Devendra B Srivastava Robyn Cotter Darlene Pedersen Ellen Collarini Shelley Izquierdo Marie-Cecile van de Lavoir W Source Type: research

LGP2 Facilitates Bacterial Escape through Binding Peptidoglycan via EEK Motif and Suppressing NOD2-RIP2 Axis in Cyprinidae and Xenocyprididae Families
J Immunol. 2024 Apr 17:ji2300800. doi: 10.4049/jimmunol.2300800. Online ahead of print.ABSTRACTRIG-I-like receptors and NOD-like receptors play pivotal roles in recognizing microbe-associated molecular patterns and initiating immune responses. The LGP2 and NOD2 proteins are important members of the RIG-I-like receptor and NOD-like receptor families, recognizing viral RNA and bacterial peptidoglycan (PGN), respectively. However, in some instances bacterial infections can induce LPG2 expression via a mechanism that remains largely unknown. In the current study, we found that LGP2 can compete with NOD2 for PGN binding and inh...
Source: Journal of Immunology - April 17, 2024 Category: Allergy & Immunology Authors: Bo Liang Wenqian Li Chunrong Yang Jianguo Su Source Type: research

Enterovirus 71 Activates Plasmacytoid Dendritic Cell-Dependent PSGL-1 Binding Independent of Productive Infection
J Immunol. 2024 Apr 17:ji2300407. doi: 10.4049/jimmunol.2300407. Online ahead of print.ABSTRACTEnterovirus 71 (EV71) is a significant causative agent of hand, foot, and mouth disease, with potential serious neurologic complications or fatal outcomes. The lack of effective treatments for EV71 infection is attributed to its elusive pathogenicity. Our study reveals that human plasmacytoid dendritic cells (pDCs), the main type I IFN-producing cells, selectively express scavenger receptor class B, member 2 (SCARB2) and P-selectin glycoprotein ligand 1 (PSGL-1), crucial cellular receptors for EV71. Some strains of EV71 can repli...
Source: Journal of Immunology - April 17, 2024 Category: Allergy & Immunology Authors: Xuyuan Zhang Zhao Yin Jialong Zhang Hao Guo Jingyun Li Xiaohua Nie Shouli Wang Liguo Zhang Source Type: research