IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation
<p dir="ltr">The activation of CD4+ T‐cells in a T cell receptor (TCR)‐dependent antigen‐specific manner is a central characteristic of the adaptive immune response. In addition to ensuring that CD4+ T‐cells recognise their cognate antigen during activation, TCR‐mediated signalling c...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , |
| منشور في: |
2024
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| _version_ | 1864513510209224704 |
|---|---|
| author | Mohammad Ameen Al‐Aghbar (19237270) |
| author2 | Meritxell Espino Guarch (18810097) Nicholas van Panhuys (14158830) |
| author2_role | author author |
| author_facet | Mohammad Ameen Al‐Aghbar (19237270) Meritxell Espino Guarch (18810097) Nicholas van Panhuys (14158830) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mohammad Ameen Al‐Aghbar (19237270) Meritxell Espino Guarch (18810097) Nicholas van Panhuys (14158830) |
| dc.date.none.fl_str_mv | 2024-06-17T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1111/imm.13821 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/IL_2_amplifies_quantitative_TCR_signalling_inputs_to_drive_Th1_and_Th2_differentiation/26389441 |
| 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 Immunology cell differentiation cytokines Th1 Th2 |
| dc.title.none.fl_str_mv | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">The activation of CD4+ T‐cells in a T cell receptor (TCR)‐dependent antigen‐specific manner is a central characteristic of the adaptive immune response. In addition to ensuring that CD4+ T‐cells recognise their cognate antigen during activation, TCR‐mediated signalling can also direct the outcome of differentiation. In both in vivo and in vitro model systems, strong TCR signalling has been demonstrated to drive Th1 differentiation, whereas weak TCR signalling drives Th2 responses. During the process of differentiation, TCR signal strength acts as a quantitative component in combination with the qualitative effects imparted by cytokines to polarise distinct T‐helper lineages. Here, we investigated the role of interleukin 2 (IL‐2) signalling in determining the outcome of TCR‐dependent differentiation. IL‐2 production was initiated as an early response to TCR‐induced activation and was regulated by the strength of TCR signalling initially received. In the absence of IL‐2, TCR dependent differentiation was found to be abolished. However, proliferative responses and early markers of activation were maintained, including the upregulation of GATA3, Tbet and Foxp3 at 24 h post‐stimulation. Demonstrating that IL‐2 signalling has a key role in stabilising and amplifying lineage‐specific transcirption factor expression during differentiation. Further, activation of IL‐2‐deficient T‐cells in the presence of exogenous cytokines was sufficient to restore differentiation whilst maintaining transcriptional signatures imparted during initial TCR signalling. Combined, our data demonstrate that the integration of quantitative TCR‐dependent signalling and qualitative IL‐2 signalling is essential for determining the fate of CD4+ T‐cells during differentiation.</p><h2>Other Information</h2><p dir="ltr">Published in: Immunology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1111/imm.13821" target="_blank">https://dx.doi.org/10.1111/imm.13821</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_ba8338b869e3ab0f754b56d72560e100 |
| identifier_str_mv | 10.1111/imm.13821 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26389441 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiationMohammad Ameen Al‐Aghbar (19237270)Meritxell Espino Guarch (18810097)Nicholas van Panhuys (14158830)Biomedical and clinical sciencesImmunologycell differentiationcytokinesTh1Th2<p dir="ltr">The activation of CD4+ T‐cells in a T cell receptor (TCR)‐dependent antigen‐specific manner is a central characteristic of the adaptive immune response. In addition to ensuring that CD4+ T‐cells recognise their cognate antigen during activation, TCR‐mediated signalling can also direct the outcome of differentiation. In both in vivo and in vitro model systems, strong TCR signalling has been demonstrated to drive Th1 differentiation, whereas weak TCR signalling drives Th2 responses. During the process of differentiation, TCR signal strength acts as a quantitative component in combination with the qualitative effects imparted by cytokines to polarise distinct T‐helper lineages. Here, we investigated the role of interleukin 2 (IL‐2) signalling in determining the outcome of TCR‐dependent differentiation. IL‐2 production was initiated as an early response to TCR‐induced activation and was regulated by the strength of TCR signalling initially received. In the absence of IL‐2, TCR dependent differentiation was found to be abolished. However, proliferative responses and early markers of activation were maintained, including the upregulation of GATA3, Tbet and Foxp3 at 24 h post‐stimulation. Demonstrating that IL‐2 signalling has a key role in stabilising and amplifying lineage‐specific transcirption factor expression during differentiation. Further, activation of IL‐2‐deficient T‐cells in the presence of exogenous cytokines was sufficient to restore differentiation whilst maintaining transcriptional signatures imparted during initial TCR signalling. Combined, our data demonstrate that the integration of quantitative TCR‐dependent signalling and qualitative IL‐2 signalling is essential for determining the fate of CD4+ T‐cells during differentiation.</p><h2>Other Information</h2><p dir="ltr">Published in: Immunology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1111/imm.13821" target="_blank">https://dx.doi.org/10.1111/imm.13821</a></p>2024-06-17T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1111/imm.13821https://figshare.com/articles/journal_contribution/IL_2_amplifies_quantitative_TCR_signalling_inputs_to_drive_Th1_and_Th2_differentiation/26389441CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/263894412024-06-17T09:00:00Z |
| spellingShingle | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation Mohammad Ameen Al‐Aghbar (19237270) Biomedical and clinical sciences Immunology cell differentiation cytokines Th1 Th2 |
| status_str | publishedVersion |
| title | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation |
| title_full | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation |
| title_fullStr | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation |
| title_full_unstemmed | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation |
| title_short | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation |
| title_sort | IL‐2 amplifies quantitative TCR signalling inputs to drive Th1 and Th2 differentiation |
| topic | Biomedical and clinical sciences Immunology cell differentiation cytokines Th1 Th2 |