Inhibition of T-cell activity in alopecia areata: recent developments and new directions
<p dir="ltr">Alopecia areata (AA) is an autoimmune disease that has a complex underlying immunopathogenesis characterized by nonscarring hair loss ranging from small bald patches to complete loss of scalp, face, and/or body hair. Although the etiopathogenesis of AA has not yet been f...
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2023
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| _version_ | 1864513507069788160 |
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| author | Thierry Passeron (6995899) |
| author2 | Brett King (10341337) Julien Seneschal (4533493) Martin Steinhoff (5340194) Ali Jabbari (137249) Manabu Ohyama (233210) Desmond J. Tobin (19483123) Simran Randhawa (19483126) Aaron Winkler (19483129) Jean-Baptiste Telliez (1776706) David Martin (3178) Alexandre Lejeune (17583823) |
| author2_role | author author author author author author author author author author author |
| author_facet | Thierry Passeron (6995899) Brett King (10341337) Julien Seneschal (4533493) Martin Steinhoff (5340194) Ali Jabbari (137249) Manabu Ohyama (233210) Desmond J. Tobin (19483123) Simran Randhawa (19483126) Aaron Winkler (19483129) Jean-Baptiste Telliez (1776706) David Martin (3178) Alexandre Lejeune (17583823) |
| author_role | author |
| dc.creator.none.fl_str_mv | Thierry Passeron (6995899) Brett King (10341337) Julien Seneschal (4533493) Martin Steinhoff (5340194) Ali Jabbari (137249) Manabu Ohyama (233210) Desmond J. Tobin (19483123) Simran Randhawa (19483126) Aaron Winkler (19483129) Jean-Baptiste Telliez (1776706) David Martin (3178) Alexandre Lejeune (17583823) |
| dc.date.none.fl_str_mv | 2023-11-06T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fimmu.2023.1243556 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Inhibition_of_T-cell_activity_in_alopecia_areata_recent_developments_and_new_directions/26830954 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Immunology Pharmacology and pharmaceutical sciences Alopecia areata autoimmune disease T cells T-cell receptor JAK inhibitor |
| dc.title.none.fl_str_mv | Inhibition of T-cell activity in alopecia areata: recent developments and new directions |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Alopecia areata (AA) is an autoimmune disease that has a complex underlying immunopathogenesis characterized by nonscarring hair loss ranging from small bald patches to complete loss of scalp, face, and/or body hair. Although the etiopathogenesis of AA has not yet been fully characterized, immune privilege collapse at the hair follicle (HF) followed by T-cell receptor recognition of exposed HF autoantigens by autoreactive cytotoxic CD8<sup>+</sup> T cells is now understood to play a central role. Few treatment options are available, with the Janus kinase (JAK) 1/2 inhibitor baricitinib (2022) and the selective JAK3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) inhibitor ritlecitinib (2023) being the only US Food and Drug Administration–approved systemic medications thus far for severe AA. Several other treatments are used off-label with limited efficacy and/or suboptimal safety and tolerability. With an increased understanding of the T-cell–mediated autoimmune and inflammatory pathogenesis of AA, additional therapeutic pathways beyond JAK inhibition are currently under investigation for the development of AA therapies. This narrative review presents a detailed overview about the role of T cells and T-cell–signaling pathways in the pathogenesis of AA, with a focus on those pathways targeted by drugs in clinical development for the treatment of AA. A detailed summary of new drugs targeting these pathways with expert commentary on future directions for AA drug development and the importance of targeting multiple T-cell–signaling pathways is also provided in this review.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2023.1243556" target="_blank">https://dx.doi.org/10.3389/fimmu.2023.1243556</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_4476addd1a2436216fb15e65d0dead1e |
| identifier_str_mv | 10.3389/fimmu.2023.1243556 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26830954 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Inhibition of T-cell activity in alopecia areata: recent developments and new directionsThierry Passeron (6995899)Brett King (10341337)Julien Seneschal (4533493)Martin Steinhoff (5340194)Ali Jabbari (137249)Manabu Ohyama (233210)Desmond J. Tobin (19483123)Simran Randhawa (19483126)Aaron Winkler (19483129)Jean-Baptiste Telliez (1776706)David Martin (3178)Alexandre Lejeune (17583823)Biomedical and clinical sciencesClinical sciencesImmunologyPharmacology and pharmaceutical sciencesAlopecia areataautoimmune diseaseT cellsT-cell receptorJAK inhibitor<p dir="ltr">Alopecia areata (AA) is an autoimmune disease that has a complex underlying immunopathogenesis characterized by nonscarring hair loss ranging from small bald patches to complete loss of scalp, face, and/or body hair. Although the etiopathogenesis of AA has not yet been fully characterized, immune privilege collapse at the hair follicle (HF) followed by T-cell receptor recognition of exposed HF autoantigens by autoreactive cytotoxic CD8<sup>+</sup> T cells is now understood to play a central role. Few treatment options are available, with the Janus kinase (JAK) 1/2 inhibitor baricitinib (2022) and the selective JAK3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) inhibitor ritlecitinib (2023) being the only US Food and Drug Administration–approved systemic medications thus far for severe AA. Several other treatments are used off-label with limited efficacy and/or suboptimal safety and tolerability. With an increased understanding of the T-cell–mediated autoimmune and inflammatory pathogenesis of AA, additional therapeutic pathways beyond JAK inhibition are currently under investigation for the development of AA therapies. This narrative review presents a detailed overview about the role of T cells and T-cell–signaling pathways in the pathogenesis of AA, with a focus on those pathways targeted by drugs in clinical development for the treatment of AA. A detailed summary of new drugs targeting these pathways with expert commentary on future directions for AA drug development and the importance of targeting multiple T-cell–signaling pathways is also provided in this review.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2023.1243556" target="_blank">https://dx.doi.org/10.3389/fimmu.2023.1243556</a></p>2023-11-06T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fimmu.2023.1243556https://figshare.com/articles/journal_contribution/Inhibition_of_T-cell_activity_in_alopecia_areata_recent_developments_and_new_directions/26830954CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/268309542023-11-06T03:00:00Z |
| spellingShingle | Inhibition of T-cell activity in alopecia areata: recent developments and new directions Thierry Passeron (6995899) Biomedical and clinical sciences Clinical sciences Immunology Pharmacology and pharmaceutical sciences Alopecia areata autoimmune disease T cells T-cell receptor JAK inhibitor |
| status_str | publishedVersion |
| title | Inhibition of T-cell activity in alopecia areata: recent developments and new directions |
| title_full | Inhibition of T-cell activity in alopecia areata: recent developments and new directions |
| title_fullStr | Inhibition of T-cell activity in alopecia areata: recent developments and new directions |
| title_full_unstemmed | Inhibition of T-cell activity in alopecia areata: recent developments and new directions |
| title_short | Inhibition of T-cell activity in alopecia areata: recent developments and new directions |
| title_sort | Inhibition of T-cell activity in alopecia areata: recent developments and new directions |
| topic | Biomedical and clinical sciences Clinical sciences Immunology Pharmacology and pharmaceutical sciences Alopecia areata autoimmune disease T cells T-cell receptor JAK inhibitor |