Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 Activation
Neuromedin U (NMU) is an evolutionarily conserved neuropeptide which was previously thought to have a proinflammatory property. Recently, it was reported that NMU induced rapid ILC2 activation and Th2 responses in allergic diseases. However, whether NMU could launch such responses in arthritis is no...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/5599439 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850234212929503232 |
|---|---|
| author | Yuanyuan Zhang Yi Qin Zhu Chen |
| author_facet | Yuanyuan Zhang Yi Qin Zhu Chen |
| author_sort | Yuanyuan Zhang |
| collection | DOAJ |
| description | Neuromedin U (NMU) is an evolutionarily conserved neuropeptide which was previously thought to have a proinflammatory property. Recently, it was reported that NMU induced rapid ILC2 activation and Th2 responses in allergic diseases. However, whether NMU could launch such responses in arthritis is not known. In this study, we investigated the effect of NMU administration on arthritis and its underlying mechanisms. C57BL/6 male mice were induced with collagen-induced arthritis (CIA) and treated with NMU-23 or PBS at an early stage of induction. NMU-23 dramatically inhibited clinical onset and severity of arthritis, accompanied with decreased bone erosion and number of osteoclasts. Mechanistically, NMU-23 administration induced the expansion of ILC2 and elevated eosinophil, IL-5, and IL-13 expression in the joint of arthritic mice. Although levels of Th2 cells are slightly increased, Gata3 expression level is also upregulated. Further, NMU-deficient (NMU-/-) mice develop less severe CIA compared with control. Interestingly, the proportion of ILC2 and FoxP3+ regulatory T cells (Treg) was elevated in NMU-/- mice. Taken together, our results reveal a previously unknown anti-inflammatory effect of NMU in CIA by inducing ILC2-Th2 activation. |
| format | Article |
| id | doaj-art-157c7c86a9364988803c8d9b4fbd2db6 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-157c7c86a9364988803c8d9b4fbd2db62025-08-20T02:02:41ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/55994395599439Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 ActivationYuanyuan Zhang0Yi Qin1Zhu Chen2Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Str. 17, Hefei 230001, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Str. 17, Hefei 230001, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Str. 17, Hefei 230001, ChinaNeuromedin U (NMU) is an evolutionarily conserved neuropeptide which was previously thought to have a proinflammatory property. Recently, it was reported that NMU induced rapid ILC2 activation and Th2 responses in allergic diseases. However, whether NMU could launch such responses in arthritis is not known. In this study, we investigated the effect of NMU administration on arthritis and its underlying mechanisms. C57BL/6 male mice were induced with collagen-induced arthritis (CIA) and treated with NMU-23 or PBS at an early stage of induction. NMU-23 dramatically inhibited clinical onset and severity of arthritis, accompanied with decreased bone erosion and number of osteoclasts. Mechanistically, NMU-23 administration induced the expansion of ILC2 and elevated eosinophil, IL-5, and IL-13 expression in the joint of arthritic mice. Although levels of Th2 cells are slightly increased, Gata3 expression level is also upregulated. Further, NMU-deficient (NMU-/-) mice develop less severe CIA compared with control. Interestingly, the proportion of ILC2 and FoxP3+ regulatory T cells (Treg) was elevated in NMU-/- mice. Taken together, our results reveal a previously unknown anti-inflammatory effect of NMU in CIA by inducing ILC2-Th2 activation.http://dx.doi.org/10.1155/2021/5599439 |
| spellingShingle | Yuanyuan Zhang Yi Qin Zhu Chen Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 Activation Journal of Immunology Research |
| title | Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 Activation |
| title_full | Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 Activation |
| title_fullStr | Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 Activation |
| title_full_unstemmed | Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 Activation |
| title_short | Neuromedin U Suppresses Collagen-Induced Arthritis through ILC2-Th2 Activation |
| title_sort | neuromedin u suppresses collagen induced arthritis through ilc2 th2 activation |
| url | http://dx.doi.org/10.1155/2021/5599439 |
| work_keys_str_mv | AT yuanyuanzhang neuromedinusuppressescollageninducedarthritisthroughilc2th2activation AT yiqin neuromedinusuppressescollageninducedarthritisthroughilc2th2activation AT zhuchen neuromedinusuppressescollageninducedarthritisthroughilc2th2activation |