The AMD-associated genetic polymorphism CFH Y402H confers vulnerability to Hydroquinone-induced stress in iPSC-RPE cells DOI Creative Commons
Angela Armento,

Inga Sonntag,

Antonio Delgado

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

Age-related macular degeneration (AMD), a degenerative disease of the macula, is caused by an interplay diverse risk factors (genetic predisposition, age and lifestyle habits). One main genetic risks includes Y402H polymorphism in complement Factor H (FH), inhibitor system activation. There has been, continues to be, much discussion around functional consequences this polymorphism, whether soluble FH protein confers its association, or if cells expressing themselves are affected alteration. In our study, we examined cell characteristics retinal pigment epithelium (RPE) cells, which play major role homeostasis stability synonymously linked AMD. Here, employ RPE derived from induced pluripotent stem (iPSC) generated donors, carrying either homozygous 402Y (low risk) 402H (high variants CFH gene. were treated with Hydroquinone (HQ), component cigarette smoke, induce oxidative damage. Intriguingly, high proved more vulnerable insult when exposed HQ, as demonstrated increased cytotoxicity caspase activation, compared low-risk cells. The exposure conditioned medium, normal human serum (NHS) inactivated NHS (iNHS) had minimal impact on nor did presence purified rescue observed effects. Considering known connection stress proteotoxic degrading processes, investigated unfolded response (UPR) autophagy. When showed increase autophagy markers; however, iPSC-RPE overall reduced autophagic flux. Our findings suggest that degree cellular susceptibility not conferred other sources, but intercellularly because corresponding predisposition. data support hypothesis less resilient stress.

Language: Английский

Complement in human disease: approved and up-and-coming therapeutics DOI Creative Commons
Erin E. West, Trent M. Woodruff, Véronique Frémeaux‐Bacchi

et al.

The Lancet, Journal Year: 2023, Volume and Issue: 403(10424), P. 392 - 405

Published: Nov. 15, 2023

Language: Английский

Citations

67
Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma DOI Open Access
Francesco Lasorsa,

Monica Rutigliano,

Martina Milella

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16515 - 16515

Published: Nov. 20, 2023

The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect organism against infections support repair damaged tissues. Alterations in this complex machinery play a role pathogenesis different diseases. Core proteins C3 C5, their activation fragments, receptors, regulators have been shown be active intracellularly as complosome. kidney is particularly vulnerable complement-induced damage, emerging findings revealed system dysregulation wide range disorders, including glomerulopathies ischemia-reperfusion injury during transplantation. Different studies that important component tumorigenesis its elements proved present TME various human malignancies. renal cell carcinoma (RCC) has recently explored. Clear papillary RCC upregulate most genes relative normal tissue. aim narrative review provide novel insights into disorders.

Language: Английский

Citations

52
From periphery to center stage: 50 years of advancements in innate immunity DOI Creative Commons
Susan Carpenter, Luke O'neill

Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2030 - 2051

Published: April 1, 2024

Over the past 50 years in field of immunology, something a Copernican revolution has happened. For long time, immunologists were mainly concerned with what is termed adaptive immunity, which involves exquisitely specific activities lymphocytes. But other arm so-called "innate immunity," had been neglected. To celebrate Cell's 50th anniversary, we have put together review processes and components innate immunity trace seminal contributions leading to modern state this field. Innate joined center interest for all those who study body's defenses, as well homeostasis pathology. We are now entering era where therapeutic targeting immune receptors downstream signals hold substantial promise infectious inflammatory diseases cancer.

Language: Английский

Citations

51
The role of complement in kidney disease DOI
Vojtěch Petr, Joshua M. Thurman

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(12), P. 771 - 787

Published: Sept. 21, 2023

Language: Английский

Citations

48
The interaction of innate immune and adaptive immune system DOI Creative Commons

Ruyuan Wang,

Caini Lan, Kamel Benlagha

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 15, 2024

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific sustained killing via B cells, T antibodies. Traditionally, it has been assumed that activates immunity; however, recent studies have revealed more complex interactions. This review a detailed dissection composition function systems, emphasizing their synergistic roles in physiological pathological contexts, providing new insights into link between these two forms immunity. Precise regulation both systems at same time is beneficial fight against immune-related diseases, for example, cGAS-STING pathway found play an important role infections cancers. In addition, paper summarizes challenges future directions field immunity, including latest single-cell sequencing technologies, CAR-T cell therapy, checkpoint inhibitors. By summarizing developments, aims enhance our understanding complexity interactions perspectives system.

Language: Английский

Citations

23
Beyond the Norm: The emerging interplay of complement system and extracellular matrix in the tumor microenvironment DOI Creative Commons
Andrea Balduit, Chiara Agostinis, Roberta Bulla

et al.

Seminars in Immunology, Journal Year: 2025, Volume and Issue: 77, P. 101929 - 101929

Published: Jan. 9, 2025

Language: Английский

Citations

5
Complement C3 of tumor-derived extracellular vesicles promotes metastasis of RCC via recruitment of immunosuppressive myeloid cells DOI Creative Commons

Yibi Zhang,

Xiaodong Wang,

Yinmin Gu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(4)

Published: Jan. 23, 2025

Heterogeneous roles of complement C3 have been implicated in tumor metastasis and are highly context dependent. However, the underlying mechanisms linking to remain elusive renal cell carcinoma (RCC). Here, we demonstrate that RCC cell-derived extracellular vesicles (EVs) contributes via polarizing tumor-associated macrophages (TAMs) into immunosuppressive phenotype recruiting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, EV induces secretion CCL2 CXCL1 by lung subsequently enhances TAM polarization PMN-MDSC recruitment. Notably, targeting CCL2/CCR2 or CXCL1/CXCR2 axis with inhibitors RS504393 Navarixin, respectively, effectively suppresses induced RCC-derived a mouse model. Clinically, patients high expression poor prognosis. Collectively, our findings reveal tumor-derived an microenvironment TAMs, thus promoting metastasis.

Language: Английский

Citations

4
Microglia undergo sex-dimorphic transcriptional and metabolic rewiring during aging DOI Creative Commons
Seokjo Kang, Emily Ko,

Amelia E. Andrews

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 5, 2024

Abstract Microglia, the brain’s resident macrophages, maintain brain homeostasis and respond to injury infection. During aging they undergo functional changes, but underlying mechanisms their contributions neuroprotection versus neurodegeneration are unclear. Previous studies suggested that microglia sex dimorphic, so we compared microglial in mice of both sexes. RNA-sequencing hippocampal revealed more aging-associated changes female than male microglia, differences old young microglia. Pathway analyses subsequent validation assays a stronger AKT-mTOR-HIF1α-driven shift glycolysis among indicated C3a production detection was elevated especially females. Recombinant induced AKT-mTOR-HIF1α signaling increased glycolytic phagocytic activity Single cell attributed dimorphism abundant disease-associated (DAM) mice, evaluation an Alzheimer’s Disease mouse model metabolic complement also apparent context neurodegenerative disease strongest neuroprotective DAM2 subset. Collectively, our data implicate autocrine C3a-C3aR reprogramming DAM during aging, females, Disease.

Language: Английский

Citations

15
The complement system as a target in cancer immunotherapy DOI Creative Commons
Nicolas S. Merle, Lubka T. Roumenina

European Journal of Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Abstract Malignant cells are part of a complex network within the tumor microenvironment, where their interaction with host and soluble mediators, including complement components, is pivotal. The system, known for its role in immune defense homeostasis, exhibits dual effect on cancer progression. This dichotomy arises from antitumoral opsonophagocytosis cytotoxicity versus protumoral chronic inflammation mediated by C5a/C5aR1 axis, influencing antitumor T‐cell responses. Recent studies have revealed distinct co‐expression patterns genes various types, correlating prognosis. Notably, some cancers exhibit co‐regulated overexpression associated poor prognosis, while others show favorable outcomes. However, significant intra‐patient heterogeneity further complicates this classification. Moreover, involvement locally produced intracellular proteins adds complexity to microenvironment dynamics. review highlights unique interplay components different patient cohorts, showing that “one size does not fit all”, cancer. It summarizes clinical trials targeting cancer, emphasizing need tailored therapeutic approaches. By elucidating mechanistic basis complement's context‐dependent role, aims facilitate development personalized therapies, ultimately improving care

Language: Английский

Citations

14
Canonical and non-canonical roles of complement in atherosclerosis DOI
Pasquale Maffia, Claudio Mauro, Ayden Case

et al.

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(11), P. 743 - 761

Published: April 10, 2024

Language: Английский

Citations

13