Genetic Reduction of IRF5 Expression after Disease Initiation Reduces Disease in a Mouse Lupus Model by Impacting Systemic and End-Organ Pathogenic Pathways DOI
Alex Pellerin, Ying Tan,

Simon Lu

et al.

The Journal of Immunology, Journal Year: 2023, Volume and Issue: 211(9), P. 1308 - 1319

Published: Sept. 18, 2023

Gain-of-function polymorphisms in the transcription factor IFN regulatory 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus. Global homozygous or heterozygous deficiency IRF5 from birth confers protection many mouse models. However, less is known about effects targeting after autoimmunity has already developed. This important point to clarify when considering as a potential therapeutic target lupus. In this study, we demonstrate that genetic reduction expression disease initiation reduces severity FcγRIIB-/- Y-linked autoimmune accelerating model. Reduction resulted decrease splenomegaly and lymphadenopathy splenic B cell activation plasmablast numbers. Splenic T differentiation were also impacted demonstrated by increase number naive CD4+ CD8+ cells memory/effector cells. Although serum antinuclear autoantibody levels not altered, led decreased immune complex deposition complement activation, diminished glomerular interstitial disease, infiltrate kidney. Mechanistically, myeloid kidney produced inflammatory cytokines TLR7 TLR9 activation. Overall, during active process sufficient reduce severity. Our data support consideration suggest approaches erythematosus may need impact activity both systemically organs.

Language: Английский

Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan DOI Creative Commons
M. Robinson, Zhoujie Ding, Mark R. Dowling

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(7), P. 1596 - 1612.e4

Published: May 9, 2023

Language: Английский

Citations

49

A guide to adaptive immune memory DOI
Nora Lam, Yoon Seung Lee, Donna L. Färber

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Language: Английский

Citations

41

Unraveling the diversity and functions of tissue-resident plasma cells DOI
Julie Tellier, Ilariya Tarasova, Junli Nie

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(2), P. 330 - 342

Published: Jan. 3, 2024

Language: Английский

Citations

20

New insights into the ontogeny, diversity, maturation and survival of long-lived plasma cells DOI
David Fooksman, Zhixin Jing, Rosa Park

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(7), P. 461 - 470

Published: Feb. 8, 2024

Language: Английский

Citations

13

Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation DOI Creative Commons
Henry J. Sutton, Xin Gao, Hannah G. Kelly

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(2), P. 245 - 255.e5

Published: Jan. 15, 2024

Language: Английский

Citations

12

B Cell Lineage in the Human Endometrium: Physiological and Pathological Implications DOI Creative Commons
Kotaro Kitaya

Cells, Journal Year: 2025, Volume and Issue: 14(9), P. 648 - 648

Published: April 29, 2025

Immunocompetent cells of B lineage function in the humoral immunity system adaptive immune responses. differentiate into plasmacytes upon antigen-induced activation and produce different subclasses immunoglobulins/antibodies. Secreted immunoglobulins not only interact with pathogens to inactivate neutralize them, but also involve complement exert antibacterial activities trigger opsonization. Endometrium is a mucosal tissue that lines mammalian uterus indispensable for establishment successful pregnancy. The lymphocytes cell are minority human cycling endometrium. Human endometrial have therefore been understudied so far. However, disorders female reproductive tract, including chronic endometritis endometriosis, highlighted importance further research on lineage. This review aims revisit lymphopoiesis, maturation, commitment, survival cells, shedding light their physiological pathological implications

Language: Английский

Citations

1

450 million years in the making: mapping the evolutionary foundations of germinal centers DOI Creative Commons
Hanover Matz, Helen Dooley

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 11, 2023

Germinal centers (GCs) are distinct microanatomical structures that form in the secondary lymphoid organs of endothermic vertebrates (i.e., mammals and some birds). Within GCs, B cells undergo a Darwinian selection process to identify clones which can respond pathogen insult as well affinity mature cell repertoire. The GC response ultimately generates memory bone marrow plasma facilitate humoral immunological memory, basis for successful vaccination programs. GCs have not been observed ectothermic jawed fishes, reptiles, amphibians). However, abundant research over past decades has indicated these organisms produce antigen specific responses degree maturation. This review examines data demonstrating fundamentals may be more conserved across vertebrate phylogeny than previously anticipated. Further, both conventional mammalian model systems comparative models raises question what evolutionary benefit provide endotherms if they seemingly unnecessary generating basic functional components adaptive immune responses.

Language: Английский

Citations

15

The origins and longevity of IgE responses as indicated by serological and cellular studies in mice and humans DOI Creative Commons
Zhoujie Ding,

Jesse Mulder,

M. Robinson

et al.

Allergy, Journal Year: 2023, Volume and Issue: 78(12), P. 3103 - 3117

Published: July 7, 2023

The existence of long-lived IgE antibody-secreting cells (ASC) is contentious, with the maintenance sensitization by continuous differentiation short-lived

Language: Английский

Citations

11

Acute malaria suppresses the B lymphocytic niche in the bone marrow through the alteration of CXCL12-abundant reticular cells DOI Creative Commons
Michelle Sue Jann Lee,

Julia Matsuo-Dapaah,

C. Zorrilla

et al.

International Immunology, Journal Year: 2024, Volume and Issue: 36(7), P. 339 - 352

Published: March 2, 2024

Bone marrow is a dynamic organ composed of stem cells that constantly receive signals from stromal and other hematopoietic in the niches bone to maintain hematopoiesis generate immune cells. Perturbation microenvironment by infection inflammation affects may affect cell development. Little known about effect malaria on govern (HSC) niche. In this study, we demonstrate mesenchymal CXCL12-abundant reticular (CAR) population reduced during acute infection. The reduction CXCL12 interleukin-7 impairs lymphopoietic niche, leading depletion common lymphoid progenitors, B mature cells, including plasma marrow. We found interferon-γ (IFNγ) responsible for upregulation Sca1 CAR yet decline populations IFNγ-independent. contrast populations, HSCs multipotent progenitors increased with expansion myelopoiesis erythropoiesis, indicating bias differentiation These findings suggest host immunity modulating

Language: Английский

Citations

4

Tuning of plasma cell lifespan by competition explains the longevity and heterogeneity of antibody persistence DOI Creative Commons
Benjamin D. Simons, Omer Karin

Immunity, Journal Year: 2024, Volume and Issue: 57(3), P. 600 - 611.e6

Published: March 1, 2024

Plasma cells that emerge after infection or vaccination exhibit heterogeneous lifespans; most survive for days to months, whereas others persist decades, providing antigen-specific long-term protection. We developed a mathematical framework explore the dynamics of plasma cell removal and its regulation by survival factors. Analyses antibody persistence following hepatitis A B HPV revealed specific patterns longevity heterogeneity within between responses, implying this process is fine-tuned near critical "flat" state two dynamic regimes. This reflects tuning rates underlying regulatory network highly sensitive variation in parameters, which amplifies lifespan differences cells. propose fine-tuning generic outcome competition over shared signals, with competition-based mechanism unifying explanation wide range experimental observations, including accumulation effects factor deletion. Our theory testable, we provide predictions.

Language: Английский

Citations

3