The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation.
Multiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). H...
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Public Library of Science (PLoS)
2022-08-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001554&type=printable |
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| author | Katie J Smith Danielle Minns Brian J McHugh Rebecca K Holloway Richard O'Connor Anna Williams Lauren Melrose Rhoanne McPherson Veronique E Miron Donald J Davidson Emily Gwyer Findlay |
| author_facet | Katie J Smith Danielle Minns Brian J McHugh Rebecca K Holloway Richard O'Connor Anna Williams Lauren Melrose Rhoanne McPherson Veronique E Miron Donald J Davidson Emily Gwyer Findlay |
| author_sort | Katie J Smith |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer-term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia, and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells, which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system. |
| format | Article |
| id | doaj-art-6092c03798ea4893825a68dc61de5313 |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2022-08-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Biology |
| spelling | doaj-art-6092c03798ea4893825a68dc61de53132025-08-20T03:44:43ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-08-01208e300155410.1371/journal.pbio.3001554The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation.Katie J SmithDanielle MinnsBrian J McHughRebecca K HollowayRichard O'ConnorAnna WilliamsLauren MelroseRhoanne McPhersonVeronique E MironDonald J DavidsonEmily Gwyer FindlayMultiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer-term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia, and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells, which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001554&type=printable |
| spellingShingle | Katie J Smith Danielle Minns Brian J McHugh Rebecca K Holloway Richard O'Connor Anna Williams Lauren Melrose Rhoanne McPherson Veronique E Miron Donald J Davidson Emily Gwyer Findlay The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation. PLoS Biology |
| title | The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation. |
| title_full | The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation. |
| title_fullStr | The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation. |
| title_full_unstemmed | The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation. |
| title_short | The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation. |
| title_sort | antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting th17 differentiation |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001554&type=printable |
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