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Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques
Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRα recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. He...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866157/ https://www.ncbi.nlm.nih.gov/pubmed/35243248 http://dx.doi.org/10.1016/j.isci.2022.103889 |
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author | Bond, Nell G. Fahlberg, Marissa D. Yu, Shan Rout, Namita Tran, Dollnovan Fitzpatrick-Schmidt, Taylor Sprehe, Lesli M. Scheef, Elizabeth A. Mudd, Joseph C. Schaub, Robert Kaur, Amitinder |
author_facet | Bond, Nell G. Fahlberg, Marissa D. Yu, Shan Rout, Namita Tran, Dollnovan Fitzpatrick-Schmidt, Taylor Sprehe, Lesli M. Scheef, Elizabeth A. Mudd, Joseph C. Schaub, Robert Kaur, Amitinder |
author_sort | Bond, Nell G. |
collection | PubMed |
description | Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRα recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. Here, we report the effects of in vivo iNKT activation in Mauritian-origin cynomolgus macaques by a humanized monoclonal antibody, NKTT320, that binds to the invariant region of the iNKT TCR. NKTT320 led to rapid iNKT activation, increased polyfunctionality, and elevation of multiple plasma analytes within 24 hours. Flow cytometry and RNA-Seq confirmed downstream activation of multiple immune subsets, enrichment of JAK/STAT and PI3K/AKT pathway genes, and upregulation of inflammation-modulating genes. NKTT320 also increased iNKT frequency in adipose tissue and did not cause iNKT anergy. Our data indicate that NKTT320 has a sustained effect on in vivo iNKT activation, potentiation of innate and adaptive immunity, and resolution of inflammation, which supports its future use as an immunotherapeutic. |
format | Online Article Text |
id | pubmed-8866157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-88661572022-03-02 Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques Bond, Nell G. Fahlberg, Marissa D. Yu, Shan Rout, Namita Tran, Dollnovan Fitzpatrick-Schmidt, Taylor Sprehe, Lesli M. Scheef, Elizabeth A. Mudd, Joseph C. Schaub, Robert Kaur, Amitinder iScience Article Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRα recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. Here, we report the effects of in vivo iNKT activation in Mauritian-origin cynomolgus macaques by a humanized monoclonal antibody, NKTT320, that binds to the invariant region of the iNKT TCR. NKTT320 led to rapid iNKT activation, increased polyfunctionality, and elevation of multiple plasma analytes within 24 hours. Flow cytometry and RNA-Seq confirmed downstream activation of multiple immune subsets, enrichment of JAK/STAT and PI3K/AKT pathway genes, and upregulation of inflammation-modulating genes. NKTT320 also increased iNKT frequency in adipose tissue and did not cause iNKT anergy. Our data indicate that NKTT320 has a sustained effect on in vivo iNKT activation, potentiation of innate and adaptive immunity, and resolution of inflammation, which supports its future use as an immunotherapeutic. Elsevier 2022-02-09 /pmc/articles/PMC8866157/ /pubmed/35243248 http://dx.doi.org/10.1016/j.isci.2022.103889 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Bond, Nell G. Fahlberg, Marissa D. Yu, Shan Rout, Namita Tran, Dollnovan Fitzpatrick-Schmidt, Taylor Sprehe, Lesli M. Scheef, Elizabeth A. Mudd, Joseph C. Schaub, Robert Kaur, Amitinder Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques |
title | Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques |
title_full | Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques |
title_fullStr | Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques |
title_full_unstemmed | Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques |
title_short | Immunomodulatory potential of in vivo natural killer T (NKT) activation by NKTT320 in Mauritian-origin cynomolgus macaques |
title_sort | immunomodulatory potential of in vivo natural killer t (nkt) activation by nktt320 in mauritian-origin cynomolgus macaques |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866157/ https://www.ncbi.nlm.nih.gov/pubmed/35243248 http://dx.doi.org/10.1016/j.isci.2022.103889 |
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