Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Imbalance between IL-36 receptor agonist and antagonist drives neutrophilic inflammation in COPD Current treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating novel therapies. Here, we show that COPD patients have increased IL-36{gamma} and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared to control subjects. IL-36{gamma} is derived mainly from small airway epithelial cells (SAEC) and further induced by a viral mimetic, whereas IL-36RA is derived from macrophages. IL-36{gamma} stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36{gamma} thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, that was inhibited by exogenous IL-36RA. The use of a therapeutic antibody that inhibits binding to the IL-36 receptor (IL-36R) attenuated IL-36{gamma} driven inflammation and cellular cross talk. We have demonstrated a novel mechanism for the amplification and propagation of neutrophilic inflammation in COPD and that blocking this cytokine family via a IL-36R neutralising antibody could be a promising new therapeutic strategy in the treatment of COPD.
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The categories of this paper are: immunology
29
The categories of this paper are: education
6
The categories of this paper are: plant
4
The categories of this paper are: neuroscience
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The categories of this paper are: epidemiology
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The categories of this paper are: genetics
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The categories of this paper are: molecular
8
The categories of this paper are: genomics
22
The categories of this paper are: physiology
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The categories of this paper are: toxicology
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The categories of this paper are: biochemistry
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The categories of this paper are: bioengineering
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The categories of this paper are: cancer
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The categories of this paper are: communication
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The categories of this paper are: animal
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The categories of this paper are: scientific