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Neuromedin U promotes human type 2 immune responses
1Respiratory Medicine Unit and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Mucosal Immunology
|July 9, 2022
Summary
Neuromedin U (NMU) promotes type 2 inflammation in humans, acting on immune cells like eosinophils. This suggests NMU contributes to diseases driven by type 2 immunity.
Area of Science:
- Immunology
- Inflammation Biology
- Respiratory Medicine
Background:
- Type 2 immunity is crucial for defense against parasites and allergens.
- Neuromedin U (NMU) is implicated as a pro-inflammatory mediator in type 2 inflammation based on animal and cell studies.
- The specific role of NMU in human type 2 immunity is not well understood.
Purpose of the Study:
- To investigate the expression of NMU and its receptor (NmUR1) in human blood and airways.
- To determine the presence and levels of NmUR1 on human immune cells, particularly type 2 immune cells.
- To elucidate the functional effects of NMU on human type 2 immune cells.
Main Methods:
- Quantification of human NMU (hNmU-25) in blood and airway samples.
- Assessment of NmU receptor 1 (NmUR1) expression on various human immune cells from blood and lung tissue.
- Functional assays to evaluate the impact of hNmU-25 on type 2 cytokine production and cell migration.
Main Results:
- hNmU-25 was detected in human blood and airways, with higher concentrations in airways.
- NmUR1 was expressed by most human immune cells, notably higher on type 2 lymphocytes (T helper, cytotoxic T cells), group-2 innate lymphoid cells, and eosinophils.
- NmUR1 expression was upregulated on lung-resident and activated type 2 immune cells.
- hNmU-25 stimulated type 2 cytokine release from type 2 lymphocytes and promoted eosinophil migration.
- hNmU-25 enhanced type 2 immune responses to other stimuli, such as prostaglandin D2.
Conclusions:
- NMU is present in human circulation and airways.
- NMU acts through NmUR1, which is expressed on key type 2 immune cells.
- NMU exhibits pro-inflammatory functions in human type 2 immunity, including cytokine induction and eosinophil recruitment.
- NMU signaling may play a significant role in the pathogenesis of human diseases associated with type 2 immunity.
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