bims-hummad 2025-11-16 papers

NeuroImmune Pharm Ther. 2025 Sep;4(3): 315-324

The promise and perils of humanized mice: workshop report from the 29th scientific conference of the society on NeuroImmune pharmacology (SNIP).

Paul W Denton, Ramesh Akkina, Howard E Gendelman, Jennifer E Koblinski, Angela Wahl, Santhi Gorantla.

On June 8, 2025, the 29th Scientific Conference of the Society on NeuroImmune Pharmacology (SNIP) hosted a workshop on the Creation, Care, and Translation of Humanized Mouse for HIV/AIDS Research. The workshop was convened by the society officers Drs. Howard E. Gendelman and Santhi Gorantla. A series of four presentations provided details about the generation, care and use of humanized mouse models. The presentation titles and presenters were: (i) "Next-Generation Humanized Mouse Models of HIV/AIDS Research" by Dr. Angela Wahl; (ii) "Advancing Humanized Mice Research Through Shared Resources" by Dr. Jennifer Koblinski; (iii) "NeuroHIV Humanized Mouse Models" by Dr. Santhi Gorantla; and (iv) "Studies on HIV Evolution, Latency, and Elite Control in Humanized Mice" by Dr. Ramesh Akkina. The presentations were followed by a discussion with workshop participants led by Dr. Paul W. Denton. Presentation summaries are provided in this report and are followed by questions offered by workshop participants alongside panel responses.

Keywords: cancer; humanized mice; immunology; infectious disease; neurology; pharmacology

DOI: https://doi.org/10.1515/nipt-2025-0014

Clin Transl Immunology. 2025 ;14(11): e70061

Adeno-associated viral vectors encoding anti-P2X7 nanobodies reduce graft-versus-host disease in a humanised mouse model.

Amal Elhage, Janna H Hadaya, Chloe Sligar, Debbie Watson, Sahil Adriouch, Ronald Sluyter.

Objectives: Graft-versus-host disease (GVHD) is an inflammatory disorder that arises following allogeneic haematopoietic stem cell transplantation. P2X7 is an extracellular ATP-gated cation channel present on immune cells. P2X7 blockade with small molecule inhibitors impairs GVHD development in a humanised mouse model. This study investigated whether adeno-associated viral (AAV) vectors encoding nanobodies (Nbs) that block mouse P2X7 (mP2X7) or both mP2X7 and human P2X7 (m/hP2X7) impair GVHD development in this model.
Methods: On Day -21, NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mice were injected intramuscularly with 10 × 1010 viral genomes encoding either green fluorescent protein (GFP), an anti-mP2X7 Nb or an anti-m/hP2X7 Nb, or with saline. On Day 0, mice were euthanised or injected intraperitoneally with 10 × 106 human peripheral blood mononuclear cells and monitored thrice weekly for signs of GVHD until the experiment or disease endpoint.
Results: The anti-m/hP2X7 and anti-mP2X7 Nbs reduced clinical GVHD and time to disease onset, as well as liver and lung GVHD. Both Nbs reduced liver human T helper (Th)17 cells. Sera collected at Day 0 and disease endpoint from treated mice, but not from control mice, completely blocked P2X7 activity in human RPMI 8226 and/or murine J774 cells, confirming circulating anti-P2X7 Nbs in mice from Day 0 to disease endpoint.
Conclusion: This study indicates that P2X7 blockade with an anti-m/hP2X7 and to a lesser extent an anti-mP2X7 Nb reduces GVHD progression in humanised mice. This supports the future testing of these P2X7 biologics as a prophylactic therapy for GVHD.

Keywords: AAVnano; adeno‐associated virus serotype 8; graft‐versus‐host disease; humanised mice; nanobodies; purinergic receptor

DOI: https://doi.org/10.1002/cti2.70061

BMC Med. 2025 Nov 12. 23(1): 631

THBS1high macrophages promote aortic aneurysm formation by orchestrating an inflammatory and smooth muscle cell phenotypic transition program in vascular Behçet's disease.

Xianting Sun, Xiufang Kong, Jun Hou, Jun Li, Kefang Guo, Yuanyuan Wei, Dan Meng, Lindi Jiang.

BACKGROUND: Vascular Behçet's disease (VBD), a representative autoimmune inflammatory disorder, is a leading cause of mortality in BD, primarily due to the formation of inflamed aneurysms. However, both the histopathological features and the underlying mechanism of VBD remain elusive. Identifying specific VBD-associated cell populations and unravel their participation within the aorta microenvironment is crucial for deciphering the pathogenesis of VBD.
METHODS: We conducted immunohistochemistry and single-cell RNA sequencing to comprehensively characterize the ascending aorta in VBD patients. Immunofluorescence staining, bulk RNA sequencing, and functional co-culture system were employed to investigate the phenotypic characteristics of pathological subsets and potential cell-cell interactions. A CaCl2-induced humanized VBD model was established to validate the transcriptomic and cellular results.
RESULTS: We identified an expansion of THBS1high macrophages in VBD, particular in active VBD. These THBS1high macrophages exhibited a proinflammatory profile and promoted the phenotypic transition of smooth muscle cells. Mechanistically, transcription factor ETS2 mediated the proinflammatory development of this macrophage subset, while tumor necrosis factor-α (TNF-α) upregulated THBS1 expression in macrophages. The adoptive transfer of THBS1high macrophages exacerbated vascular inflammation and aneurysm formation in CaCl2-induced humanized VBD mice, which could be mitigated by TNF inhibitor. Clinically, plasma THBS1 levels were positively correlated with disease activity and inversely associated with the clinical benefits of TNF inhibitor, both observed at the systemic level.
CONCLUSIONS: Overall, our findings underscore the pivotal role of THBS1high macrophages in vascular degeneration, highlighting the therapeutic potential of anti-TNF therapy in VBD and the THBS1's potential as a biomarker for clinical evaluation.

Keywords: Macrophages; Single-cell RNA sequencing; THBS1; Tumor necrosis factor; Vascular Behçet’s disease

DOI: https://doi.org/10.1186/s12916-025-04434-y