Evolutionary Divergence in Human Versus Mouse Innate Immune Gene Regulation and Function

Kapétanovic, Ronan; Ariffin, Juliana K.; Sweet, Matthew J.

doi:10.1007/978-3-319-07623-2_6

Cited by 3 publications

(3 citation statements)

References 240 publications

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“…Although the mouse genome is somewhat smaller than the human, eighty percent (80%) of mouse coding sequences have direct (1:1) orthologs in the human genome, with most of the remaining divergence related to species‐specific gene clusters . At the same time, it is critical to recognize that the immune system evolves under distinct, likely pathogen‐directed external constraints, which may differ even between closely related species given distinct environments and habitats.…”

Section: Animal Models Of Human Disease: General Considerationsmentioning

confidence: 99%

Modeling asthma: Pitfalls, promises, and the road ahead

Rosenberg

Druey

2018

Journal of Leukocyte Biology

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Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung size, structure, and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource.

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Section: Animal Models Of Human Disease: General Considerationsmentioning

confidence: 99%

Modeling asthma: Pitfalls, promises, and the road ahead

Rosenberg

Druey

2018

Journal of Leukocyte Biology

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“…The challenges of studying inflammasome phosphorylation include the lack of well characterised phospho-specific antibodies, differences in mouse and human cell models, and the translation of in vitro identified phospho-sites to in vivo disease relevance (e.g. NLRC4 Ser533) [ 99 , 100 ]. Despite these obstacles there are already reports using specific kinase inhibitors to modulate inflammasomes in vivo .…”

Section: Discussionmentioning

confidence: 99%

PHOrming the inflammasome: phosphorylation is a critical switch in inflammasome signalling

McKee

Fischer

Bezbradica

et al. 2021

Biochemical Society Transactions

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Inflammasomes are protein complexes in the innate immune system that regulate the production of pro-inflammatory cytokines and inflammatory cell death. Inflammasome activation and subsequent cell death often occur within minutes to an hour, so the pathway must be dynamically controlled to prevent excessive inflammation and the development of inflammatory diseases. Phosphorylation is a fundamental post-translational modification that allows rapid control over protein function and the phosphorylation of inflammasome proteins has emerged as a key regulatory step in inflammasome activation. Phosphorylation of inflammasome sensor and adapter proteins regulates their inter- and intra-molecular interactions, subcellular localisation, and function. The control of inflammasome phosphorylation may thus provide a new strategy for the development of anti-inflammatory therapeutics. Herein we describe the current knowledge of how phosphorylation operates as a critical switch for inflammasome signalling.

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“…In particular, POPs, COPs, and alternative splicing may significantly influence NLRP3 activation in human cells. In addition, there is an appreciable divergence between innate immune signaling pathways in human and mouse cells 147,148 that may affect how stimuli such as LPS trigger NLRP3 priming.…”

Section: Concluding Remarks and Open Questionsmentioning

confidence: 99%

NLRP3 inflammasome priming: A riddle wrapped in a mystery inside an enigma

McKee

Coll

2020

Journal of Leukocyte Biology

129

138

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The NLRP3 (NOD‐, LRR‐, and pyrin domain‐containing protein 3) inflammasome is an immunological sensor that detects a wide range of microbial‐ and host‐derived signals. Inflammasome activation results in the release of the potent pro‐inflammatory cytokines IL‐1β and IL‐18 and triggers a form of inflammatory cell death known as pyroptosis. Excessive NLRP3 activity is associated with the pathogenesis of a wide range of inflammatory diseases, thus NLRP3 activation mechanisms are an area of intensive research. NLRP3 inflammasome activation is a tightly regulated process that requires both priming and activation signals. In particular, recent research has highlighted the highly complex nature of the priming step, which involves transcriptional and posttranslational mechanisms, and numerous protein binding partners. This review will describe the current understanding of NLRP3 priming and will discuss the potential opportunities for targeting this process therapeutically to treat NLRP3‐associated diseases.

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Evolutionary Divergence in Human Versus Mouse Innate Immune Gene Regulation and Function

Cited by 3 publications

References 240 publications

Modeling asthma: Pitfalls, promises, and the road ahead

Modeling asthma: Pitfalls, promises, and the road ahead

PHOrming the inflammasome: phosphorylation is a critical switch in inflammasome signalling

NLRP3 inflammasome priming: A riddle wrapped in a mystery inside an enigma

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