DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling
Dendritic cell immunoreceptor (DCIR) is an inhibitory C-type lectin receptor that acts as a negative regulator in the immune system and bone metabolism. We previously revealed that DCIR deficiency enhanced osteoclastogenesis and antigen presentation of dendritic cells, and that asialo-biantennary N-...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1159058/full |
| _version_ | 1827946147764764672 |
|---|---|
| author | Tomonori Kaifu Takumi Maruhashi Soo-Hyun Chung Kenji Shimizu Akira Nakamura Yoichiro Iwakura |
| author_facet | Tomonori Kaifu Takumi Maruhashi Soo-Hyun Chung Kenji Shimizu Akira Nakamura Yoichiro Iwakura |
| author_sort | Tomonori Kaifu |
| collection | DOAJ |
| description | Dendritic cell immunoreceptor (DCIR) is an inhibitory C-type lectin receptor that acts as a negative regulator in the immune system and bone metabolism. We previously revealed that DCIR deficiency enhanced osteoclastogenesis and antigen presentation of dendritic cells, and that asialo-biantennary N-glycan (NA2) functions as a ligand for DCIR. NA2 binding to DCIR suppressed murine and human osteoclastogenesis that occurs in the presence of M-CSF and RANKL. The DCIR-NA2 axis, therefore, plays an important role in regulating osteoclastogenesis in both mice and humans, although the underlying mechanisms remain unclear. Here we found that Dcir−/− bone marrow–derived macrophages (BMMs) exhibited greater proliferative and differentiation responses to M-CSF and RANKL, respectively, than wild-type (WT) BMMs. Moreover, Dcir−/− osteoclasts (OCs) increased resorptive activity and cell fusion more significantly than WT OCs. DCIR deficiency affects gene expression patterns in OCs, and we found that the expression of neuraminidase 4 was increased in Dcir−/− OCs. Furthermore, DCIR-NA2 interaction in WT BMMs, but not Dcir−/− BMMs, decreased Akt phosphorylation in response to M-CSF and RANKL. These data suggest that DCIR regulates osteoclastogenesis by downregulating M-CSF and RANKL signaling, and that DCIR-mediated signaling may contribute to the terminal modification of oligosaccharides by controlling the expression of glycosylation enzymes. |
| first_indexed | 2024-03-13T10:54:36Z |
| format | Article |
| id | doaj.art-abeeffd923b04c9b8238870d97abdd04 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T10:54:36Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-abeeffd923b04c9b8238870d97abdd042023-05-17T05:41:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11590581159058DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signalingTomonori Kaifu0Takumi Maruhashi1Soo-Hyun Chung2Kenji Shimizu3Akira Nakamura4Yoichiro Iwakura5Division of Immunology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, JapanLaboratory of Molecular Immunology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, JapanCenter for Animal Disease Models, Research Institution for Biological Sciences, Tokyo University of Science, Noda, Chiba, JapanLaboratory of Molecular Immunology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, JapanDivision of Immunology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, JapanCenter for Animal Disease Models, Research Institution for Biological Sciences, Tokyo University of Science, Noda, Chiba, JapanDendritic cell immunoreceptor (DCIR) is an inhibitory C-type lectin receptor that acts as a negative regulator in the immune system and bone metabolism. We previously revealed that DCIR deficiency enhanced osteoclastogenesis and antigen presentation of dendritic cells, and that asialo-biantennary N-glycan (NA2) functions as a ligand for DCIR. NA2 binding to DCIR suppressed murine and human osteoclastogenesis that occurs in the presence of M-CSF and RANKL. The DCIR-NA2 axis, therefore, plays an important role in regulating osteoclastogenesis in both mice and humans, although the underlying mechanisms remain unclear. Here we found that Dcir−/− bone marrow–derived macrophages (BMMs) exhibited greater proliferative and differentiation responses to M-CSF and RANKL, respectively, than wild-type (WT) BMMs. Moreover, Dcir−/− osteoclasts (OCs) increased resorptive activity and cell fusion more significantly than WT OCs. DCIR deficiency affects gene expression patterns in OCs, and we found that the expression of neuraminidase 4 was increased in Dcir−/− OCs. Furthermore, DCIR-NA2 interaction in WT BMMs, but not Dcir−/− BMMs, decreased Akt phosphorylation in response to M-CSF and RANKL. These data suggest that DCIR regulates osteoclastogenesis by downregulating M-CSF and RANKL signaling, and that DCIR-mediated signaling may contribute to the terminal modification of oligosaccharides by controlling the expression of glycosylation enzymes.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1159058/fullC-type lectin receptorosteoclastcytokinesoligosaccharideshomeostasismetabolism |
| spellingShingle | Tomonori Kaifu Takumi Maruhashi Soo-Hyun Chung Kenji Shimizu Akira Nakamura Yoichiro Iwakura DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling Frontiers in Immunology C-type lectin receptor osteoclast cytokines oligosaccharides homeostasis metabolism |
| title | DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling |
| title_full | DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling |
| title_fullStr | DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling |
| title_full_unstemmed | DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling |
| title_short | DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling |
| title_sort | dcir suppresses osteoclastic proliferation and resorption by downregulating m csf and rankl signaling |
| topic | C-type lectin receptor osteoclast cytokines oligosaccharides homeostasis metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1159058/full |
| work_keys_str_mv | AT tomonorikaifu dcirsuppressesosteoclasticproliferationandresorptionbydownregulatingmcsfandranklsignaling AT takumimaruhashi dcirsuppressesosteoclasticproliferationandresorptionbydownregulatingmcsfandranklsignaling AT soohyunchung dcirsuppressesosteoclasticproliferationandresorptionbydownregulatingmcsfandranklsignaling AT kenjishimizu dcirsuppressesosteoclasticproliferationandresorptionbydownregulatingmcsfandranklsignaling AT akiranakamura dcirsuppressesosteoclasticproliferationandresorptionbydownregulatingmcsfandranklsignaling AT yoichiroiwakura dcirsuppressesosteoclasticproliferationandresorptionbydownregulatingmcsfandranklsignaling |