CITIID research highlights from the last 6 months.
For help with promoting your research, please contact comms@med.cam.ac.uk
'GPR35 prevents osmotic stress induced cell damage'
Authors: Joshua E Elias, Mekdes Debela, Gavin W Sewell, Richard J Stopforth, Hannah Partl, Sophie Heissbauer, Lorraine M Holland, Tom H Karlsen, Arthur Kaser, Nicole C Kaneider
Communications Biology. 2025 Mar 22;8(1):478, https://doi.org/10.1038/s42003-025-07848-9
'RNA binding by Periphilin plays an essential role in initiating silencing by the HUSH complex'
Authors: Stuart Bloor, Niek Wit, Paul J Lehner
Nucleic Acids Research, Volume 53, Issue 2, 27 January 2025, gkae1165, https://doi.org/10.1093/nar/gkae1165
'Temporal profiling of human lymphoid tissues reveals coordinated defense against viral challenge'
Authors: Matthew L. Coates, Nathan Richoz, Zewen K. Tuong, Georgina S. Bowyer, Colin Y. C. Lee, John R. Ferdinand, Eleanor Gillman, Mark McClure, Lisa Dratva, Sarah A. Teichmann, David R. Jayne, Rafael Di Marco Barros, Benjamin J. Stewart, Menna R. Clatworthy
Nature Immunology. 2025 Feb;26(2):215-29, https://doi.org/10.1038/s41590-024-02064-9
'Structure and Methyl-lysine Binding Selectivity of the HUSH Complex Subunit MPP8'
Authors: Nikos Nikolopoulos, Shun-Ichiro Oda, Daniil M Prigozhin, Yorgo Modis
HUSH is a transcriptional repressor complex that guards the genome from retroelements. Our structures of HUSH components TASOR and MPP8 reveal similarities to SPOC domains and SUMO E3 ligases. A domain with a novel fold in TASOR is required for HUSH function. We found that MPP8, which is known to bind the repressive mark H3K9me3, also bound the H3K9 methyltransferase SETDB1/ATF7IP. Our work suggests a read-write mechanism for amplification of the transcriptionally repressive epigenetic mark H3K9me3 to prevent transposable elements from taking over our genome.
Journal of Molecular Biology. 2025 Jan 15;437(2):168890, https://doi.org/10.1016/j.jmb.2024.168890
'Loss-of-function mutations in the dystonia gene THAP1 impair proteasome function by inhibiting PSMB5 expression'
Authors: Dylan E. Ramage, Drew W. Grant, Richard T. Timms
Nature Communications. 2025 Feb 10;16(1):1511, https://doi.org/10.1038/s41467-025-56782-1
'Humoral responses to SARS-CoV-2 vaccine in vasculitis-related immune suppression'
Authors: Kamelian K, Sievers B, Chen-Xu M, Turner S, Tsz Kin Cheng M, Altaf M, Kemp S.A, Abdullahi A, Csiba K, Collier D.A., Mlcochova P, Meng B, Jones R.B, The CITIID-NIHR BioResource COVID-19 Collaboration, Smith D, Bradley J, Smith K.G. C, Doffinger R, Smith R. M, and Gupta R.K
Sci Adv; 12 Feb 2025; DOI: 10.1126/sciadv.adq3342
'Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses'
Authors: Sardar P, Beresford-Jones B.S., Xia W, Shabana O, Suyama S, Ramos R. J. F, Soderholm A.T, Tourlomousis P, Kuo P, Evans A.C, Imianowski C.J, Conti A.G, Wesolowski A.J, Baker N.M., McCord E. A. L., Okkenhaug K, Whiteside S. K., Roychoudhuri R, Bryant C. E., Cross J. R. & Pedicord V. A.
Nat Microbiol 10, 795–807 (2025).
'Macrophages and nociceptor neurons form a sentinel unit around fenestrated capillaries to defend the synovium from circulating immune challenge'
Published 25 November 2024 in Nature Immunology.
Authors: Tetsuo Hasegawa, Colin Y. C. Lee, Andrew J. Hotchen, Aaron Fleming, Rahul Singh,Kunimichi Suzuki, Michisuke Yuzaki, Masahiko Watanabe, Mark A. Birch, Andrew W. McCaskie, Nikolett Lénárt, Krisztina Tóth, Ádám Dénes, Zhaoyuan Liu, Florent Ginhoux, Nathan Richoz & Menna R. Clatworthy
Nature Immunology 25, 2270–2283 (2024). DOI: 10.1038/s41590-024-02011-8
‘Long-term surveillance study of rituximab originator treated patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)’
Published on 6 August 2024 in Rheumatology Advances in Practice.
Authors: Uchida L, Jones RB, Smith RM, Nodale M, Bond S, Loechel C, King M,Luqmani R, Gray D, Barrett J, Jayne DRW.
Rheumatology Advances in Practice, Volume 8,Issue 3, 2024, rkae090, https://doi.org/10.1093/rap/rkae090
Occurrence of human infection with Salmonella Typhi in sub-Saharan Africa
Authors: Kim JH, Parajulee P, Nguyen TT, Wasunkar S, Mogasale V,Park SE, Panzner U, Mogeni OD, Im J, Marks F.
Scientific Data volume 11, Article number: 1089 (2024)
Sci Data. 2024 Oct 5;11(1):1089. DOI:10.1038/s41597-024-03912-x.
‘Neutrophil extracellular traps protect the kidney from ascending infection and are required for a positive leukocyte dipstick test’
Published 25 September 2024 in Science Translational Medicine.
Authors: Andrew P.Stewart, Kevin W. Loudon, Matthew Routledge, Colin Y.C. Lee, Patrick Trotter, Nathan Richoz, Eleanor Gillman, Robin Antrobus, James Mccaffrey, David Posner, Andrew Conway Morris, Fiona E. Karet Frankl, and Menna R. Clatworthy.
Stewart et al. identify neutrophil extracellular traps (NETs) in healthy human urine that provide antibacterial defence within the urinary tract. Inhibition of NETosis in mice resulted in progression of cystitis into pyelonephritis, implicating NETosis of urinary neutrophils as a key mechanism that prevents bacterial ascent into the kidney.
They also found that urine dipstick testing for leukocyte esterase does not detect absolute neutrophil count, as has long been assumed, but rather neutrophils that have undergone NETosis.
Science Translational Medicine, 25 Sep 2024, Vol 16, Issue 766, DOI: 10.1126/scitranslmed.adh5090
‘Leveraging pleiotropy identifies common-variantassociations with selective IgA deficiency’
Authors: Thomas W. Willis, Effrossyni Gkrania-Klotsas, Nicholas J. Wareham, Eoin F. McKinney, Paul A. Lyons, Kenneth G.C. Smith, Chris Wallace
Through assembling large meta genome-wide association studies and employing cross-phenotype analysis methods, we identified 18 novel associations between common genetic variation and selective IgA deficiency. Genes near these associations should be assessed as potentially causal for more severe inborn errors of immunity in patients who do not yet have a genetic diagnosis.
Clinical Immunology, Volume 268,November 2024, 110356 doi:10.1016/j.clim.2024.110356.
