Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis.
The cysteine cathepsins B, S, and L are functionally linked to antigen processing, and hence to autoimmune disorders such as multiple sclerosis. Stemming from several studies that demonstrate that mice can be protected from experimental autoimmune encephalomyelitis (EAE) through the pharmacologic in...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4468166?pdf=render |
| _version_ | 1818532915053592576 |
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| author | Euan Ramsay Orr Allan Robin Michael Yates |
| author_facet | Euan Ramsay Orr Allan Robin Michael Yates |
| author_sort | Euan Ramsay Orr Allan |
| collection | DOAJ |
| description | The cysteine cathepsins B, S, and L are functionally linked to antigen processing, and hence to autoimmune disorders such as multiple sclerosis. Stemming from several studies that demonstrate that mice can be protected from experimental autoimmune encephalomyelitis (EAE) through the pharmacologic inhibition of cysteine cathepsins, it has been suggested that targeting these enzymes in multiple sclerosis may be of therapeutic benefit. Utilizing mice deficient in cysteine cathepsins both individually and in combination, we found that the myelin-associated antigen myelin oligodendrocyte glycoprotein (MOG) was efficiently processed and presented by macrophages to CD4+ T cells in the individual absence of cathepsin B, S or L. Similarly, mice deficient in cathepsin B or S were susceptible to MOG-induced EAE and displayed clinical progression and immune infiltration into the CNS, similar to their wild-type counterparts. Owing to a previously described CD4+ T cell deficiency in mice deficient in cathepsin L, such mice were protected from EAE. When multiple cysteine cathepsins were simultaneously inhibited via genetic deletion of both cathepsins B and S, or by a cathepsin inhibitor (LHVS), MHC-II surface expression, MOG antigen presentation and EAE were attenuated or prevented. This study demonstrates the functional redundancy between cathepsin B, S and L in EAE, and suggests that the inhibition of multiple cysteine cathepsins may be needed to modulate autoimmune disorders such as multiple sclerosis. |
| first_indexed | 2024-12-11T17:51:46Z |
| format | Article |
| id | doaj.art-5364e9f8636648da800b996c3b37f44d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T17:51:46Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5364e9f8636648da800b996c3b37f44d2022-12-22T00:56:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012894510.1371/journal.pone.0128945Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis.Euan Ramsay Orr AllanRobin Michael YatesThe cysteine cathepsins B, S, and L are functionally linked to antigen processing, and hence to autoimmune disorders such as multiple sclerosis. Stemming from several studies that demonstrate that mice can be protected from experimental autoimmune encephalomyelitis (EAE) through the pharmacologic inhibition of cysteine cathepsins, it has been suggested that targeting these enzymes in multiple sclerosis may be of therapeutic benefit. Utilizing mice deficient in cysteine cathepsins both individually and in combination, we found that the myelin-associated antigen myelin oligodendrocyte glycoprotein (MOG) was efficiently processed and presented by macrophages to CD4+ T cells in the individual absence of cathepsin B, S or L. Similarly, mice deficient in cathepsin B or S were susceptible to MOG-induced EAE and displayed clinical progression and immune infiltration into the CNS, similar to their wild-type counterparts. Owing to a previously described CD4+ T cell deficiency in mice deficient in cathepsin L, such mice were protected from EAE. When multiple cysteine cathepsins were simultaneously inhibited via genetic deletion of both cathepsins B and S, or by a cathepsin inhibitor (LHVS), MHC-II surface expression, MOG antigen presentation and EAE were attenuated or prevented. This study demonstrates the functional redundancy between cathepsin B, S and L in EAE, and suggests that the inhibition of multiple cysteine cathepsins may be needed to modulate autoimmune disorders such as multiple sclerosis.http://europepmc.org/articles/PMC4468166?pdf=render |
| spellingShingle | Euan Ramsay Orr Allan Robin Michael Yates Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis. PLoS ONE |
| title | Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis. |
| title_full | Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis. |
| title_fullStr | Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis. |
| title_full_unstemmed | Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis. |
| title_short | Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis. |
| title_sort | redundancy between cysteine cathepsins in murine experimental autoimmune encephalomyelitis |
| url | http://europepmc.org/articles/PMC4468166?pdf=render |
| work_keys_str_mv | AT euanramsayorrallan redundancybetweencysteinecathepsinsinmurineexperimentalautoimmuneencephalomyelitis AT robinmichaelyates redundancybetweencysteinecathepsinsinmurineexperimentalautoimmuneencephalomyelitis |