IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8
Background: Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as a dual-function cytokine in that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to the nucleus. However, whether...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:235451 |
| Acceso en línea: | https://ddd.uab.cat/record/235451 https://dx.doi.org/urn:doi:10.7150/thno.47435 |
| Access Level: | acceso abierto |
| Palabra clave: | Multiple sclerosis Experimental autoimmune encephalomyelitis IL-37 IL-1R8 Cytokines |
| id |
ES_31cbd6d5ac1e424d6c821caa4d4d3df2 |
|---|---|
| oai_identifier_str |
oai:ddd.uab.cat:235451 |
| network_acronym_str |
ES |
| network_name_str |
España |
| spelling |
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8 Sánchez Fernández, Alba Zandee, Stephanie|||0000-0003-0812-676X Amo Aparicio, Jesús|||0000-0002-1294-6819 Charabati, Marc|||0000-0002-4595-1040 Prat, Alexandre|||0000-0001-6188-0580 Garlanda, Cecilia Eisenmesser, Elan Z. Dinarello, Charles A. López Vales, Rubén|||0000-0001-7615-9550 Multiple sclerosis Experimental autoimmune encephalomyelitis IL-37 IL-1R8 Cytokines Background: Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as a dual-function cytokine in that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to the nucleus. However, whether IL-37 exerts beneficial actions in neuroinflammatory diseases, such as multiple sclerosis, remains to be elucidated. Thus, the goals of the present study were to evaluate the therapeutic effects of IL-37 in a mouse model of multiple sclerosis, and if so, whether this is mediated via the extracellular receptor complex IL-1R5/IL-1R8. Methods: We used a murine model of MS, the experimental autoimmune encephalomyelitis (EAE). We induced EAE in three different single and double transgenic mice (hIL-37tg, IL-1R8 KO, hIL-37tg-IL-1R8 KO) and wild type littermates. We also induced EAE in C57Bl/6 mice and treated them with various forms of recombinant human IL-37 protein. Functional and histological techniques were used to assess locomotor deficits and demyelination. Luminex and flow cytometry analysis were done to assess the protein levels of pro-inflammatory cytokines and different immune cell populations, respectively. qPCRs were done to assess the expression of IL-37, IL-1R5 and IL-1R8 in the spinal cord of EAE, and in blood peripheral mononuclear cells and brain tissue samples of MS patients. Results: We demonstrate that IL-37 reduces inflammation and protects against neurological deficits and myelin loss in EAE mice by acting via IL1-R5/IL1-R8. We also reveal that administration of recombinant human IL-37 exerts therapeutic actions in EAE mice. We finally show that IL-37 transcripts are not up-regulated in peripheral blood mononuclear cells and in brain lesions of MS patients, despite the IL-1R5/IL-1R8 receptor complex is expressed. Conclusions: This study presents novel data indicating that IL-37 exerts therapeutic effects in EAE by acting through the extracellular receptor complex IL-1R5/IL-1R8, and that this protective physiological mechanism is defective in MS individuals. IL-37 may therefore represent a novel therapeutic avenue for the treatment of MS with great promising potential. https://ddd.uab.cat/record/235451 https://dx.doi.org/urn:doi:10.7150/thno.47435 |
| title |
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8 |
| spellingShingle |
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8 Sánchez Fernández, Alba Multiple sclerosis Experimental autoimmune encephalomyelitis IL-37 IL-1R8 Cytokines |
| title_short |
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8 |
| title_full |
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8 |
| title_fullStr |
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8 |
| title_full_unstemmed |
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8 |
| title_sort |
IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8 |
| author |
Sánchez Fernández, Alba |
| author_facet |
Sánchez Fernández, Alba Zandee, Stephanie|||0000-0003-0812-676X Amo Aparicio, Jesús|||0000-0002-1294-6819 Charabati, Marc|||0000-0002-4595-1040 Prat, Alexandre|||0000-0001-6188-0580 Garlanda, Cecilia Eisenmesser, Elan Z. Dinarello, Charles A. López Vales, Rubén|||0000-0001-7615-9550 |
| author_role |
author |
| author2 |
Zandee, Stephanie|||0000-0003-0812-676X Amo Aparicio, Jesús|||0000-0002-1294-6819 Charabati, Marc|||0000-0002-4595-1040 Prat, Alexandre|||0000-0001-6188-0580 Garlanda, Cecilia Eisenmesser, Elan Z. Dinarello, Charles A. López Vales, Rubén|||0000-0001-7615-9550 |
| author2_role |
author author author author author author author author |
| topic |
Multiple sclerosis Experimental autoimmune encephalomyelitis IL-37 IL-1R8 Cytokines |
| topic_facet |
Multiple sclerosis Experimental autoimmune encephalomyelitis IL-37 IL-1R8 Cytokines |
| description |
Background: Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as a dual-function cytokine in that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to the nucleus. However, whether IL-37 exerts beneficial actions in neuroinflammatory diseases, such as multiple sclerosis, remains to be elucidated. Thus, the goals of the present study were to evaluate the therapeutic effects of IL-37 in a mouse model of multiple sclerosis, and if so, whether this is mediated via the extracellular receptor complex IL-1R5/IL-1R8. Methods: We used a murine model of MS, the experimental autoimmune encephalomyelitis (EAE). We induced EAE in three different single and double transgenic mice (hIL-37tg, IL-1R8 KO, hIL-37tg-IL-1R8 KO) and wild type littermates. We also induced EAE in C57Bl/6 mice and treated them with various forms of recombinant human IL-37 protein. Functional and histological techniques were used to assess locomotor deficits and demyelination. Luminex and flow cytometry analysis were done to assess the protein levels of pro-inflammatory cytokines and different immune cell populations, respectively. qPCRs were done to assess the expression of IL-37, IL-1R5 and IL-1R8 in the spinal cord of EAE, and in blood peripheral mononuclear cells and brain tissue samples of MS patients. Results: We demonstrate that IL-37 reduces inflammation and protects against neurological deficits and myelin loss in EAE mice by acting via IL1-R5/IL1-R8. We also reveal that administration of recombinant human IL-37 exerts therapeutic actions in EAE mice. We finally show that IL-37 transcripts are not up-regulated in peripheral blood mononuclear cells and in brain lesions of MS patients, despite the IL-1R5/IL-1R8 receptor complex is expressed. Conclusions: This study presents novel data indicating that IL-37 exerts therapeutic effects in EAE by acting through the extracellular receptor complex IL-1R5/IL-1R8, and that this protective physiological mechanism is defective in MS individuals. IL-37 may therefore represent a novel therapeutic avenue for the treatment of MS with great promising potential. |
| publishDate |
2021 |
| format |
article |
| url |
https://ddd.uab.cat/record/235451 https://dx.doi.org/urn:doi:10.7150/thno.47435 |
| language |
eng |
| eu_rights_str_mv |
openAccess |
| institution |
Universitat Autònoma de Barcelona |
| collection |
Dipòsit Digital de Documents de la UAB |
| reponame_str |
Dipòsit Digital de Documents de la UAB |
| instname_str |
Universitat Autònoma de Barcelona |
| _version_ |
1878433123829547008 |
| publishDateSort |
2021 |
| author_browse |
Amo Aparicio, Jesús|||0000-0002-1294-6819 Charabati, Marc|||0000-0002-4595-1040 Dinarello, Charles A. Eisenmesser, Elan Z. Garlanda, Cecilia López Vales, Rubén|||0000-0001-7615-9550 Prat, Alexandre|||0000-0001-6188-0580 Sánchez Fernández, Alba Zandee, Stephanie|||0000-0003-0812-676X |
| score |
6,9489965 |