Karen J. Mackenzie

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Aicardi-Goutières syndrome (AGS) provides a monogenic model of nucleic acid-mediated inflammation relevant to the pathogenesis of systemic autoimmunity. Mutations that impair ribonuclease (RNase) H2 enzyme function are the most frequent cause of this autoinflammatory disorder of childhood and are also associated with systemic lupus erythematosus. Reduced(More)
Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also known as antimicrobial peptides) and an important component of innate host defence against infection. In addition to microbicidal potential, these peptides have properties with the capacity to modulate inflammation and immunity. However, the extent to which such properties play a(More)
Eosinophilic granulocytes are innate effector cells that are important in immune responses against helminth parasitic infections and contribute towards the pathology associated with allergic inflammatory conditions, including allergic rhinitis and asthma. Their recruitment to inflammatory sites occurs in response to chemotactic and activation signals, such(More)
We have assessed the complexity in T cell recognition of the immunodominant 35-55 region of myelin oligodendrocyte glycoprotein (MOG) in C57BL/6 mice. Immunization with the p35-55 peptide generated two types of T cell, recognizing either a cryptic, or a naturally-processed epitope. Clear differences in the recognition of residues within a core sequence of(More)
DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal(More)
The sensing of nucleic acids by receptors of the innate immune system is a key component of antimicrobial immunity. RNA:DNA hybrids, as essential intracellular replication intermediates generated during infection, could therefore represent a class of previously uncharacterised pathogen-associated molecular patterns sensed by pattern recognition receptors.(More)
Peptide immunotherapy (PIT) offers realistic prospects for the treatment of allergic diseases, including allergic asthma. Much is understood of the behavior of naive T cells in response to PIT. However, treatment of patients with ongoing allergic disease requires detailed understanding of the responses of allergen-experienced T cells. CD62L expression by(More)
Compaction of chromosomes is essential for accurate segregation of the genome during mitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here, we report that biallelic mutations in NCAPD2, NCAPH, or NCAPD3, encoding subunits of these(More)
Peptide immunotherapy using soluble peptides containing allergen-derived immunodominant T-cell epitopes holds therapeutic promise for allergic asthma. Previous studies in BALB/c mice using the immunodominant peptide epitope of chicken ovalbumin (p323-339) have been unable to demonstrate therapeutic effects in ovalbumin-induced allergic airway inflammation.(More)
Viral lower respiratory tract infection (LRTI) can lead to severe disease at all ages, but with the exception of influenza vaccination, prevention is not available for most respiratory viruses, hence, effective, disease-limiting therapy is urgently required. To enable the development of novel effective therapeutic approaches, we need to improve(More)