Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2.
The transcription factors mediating the development of CD1d-restricted invariant NKT (iNKT) cells remain incompletely described. Here, we show that loss of the AP-1 transcription factor Fra-2 causes a marked increase in the number of both thymic and peripheral iNKT cells, without affecting the devel...
| Main Authors: | , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2009
|
| _version_ | 1797073584055648256 |
|---|---|
| author | Lawson, V Maurice, D Silk, J Cerundolo, V Weston, K |
| author_facet | Lawson, V Maurice, D Silk, J Cerundolo, V Weston, K |
| author_sort | Lawson, V |
| collection | OXFORD |
| description | The transcription factors mediating the development of CD1d-restricted invariant NKT (iNKT) cells remain incompletely described. Here, we show that loss of the AP-1 transcription factor Fra-2 causes a marked increase in the number of both thymic and peripheral iNKT cells, without affecting the development of other T-lineage cells. The defect is cell-autonomous and is evident in the earliest iNKT precursors. We find that iNKT cells expressing the lower affinity TCRVbeta8 are proportionally overrepresented in the absence of Fra-2, indicating altered selection of iNKT cells. There is also widespread dysregulation of AP-1-directed gene expression. In the periphery, mature Fra-2-deficient iNKT cells are able to participate in an immune response, but they have an altered response to Ag, showing increased expansion and producing increased amounts of IL-2 and IL-4 compared with their wild-type counterparts. Unusually, naive Fra-2-deficient T cells also rapidly produce IL-2 and IL-4 upon activation. Taken together, these data define Fra-2 as necessary for regulation of normal iNKT cell development and function, and they demonstrate the central role played by the AP-1 family in this lineage. |
| first_indexed | 2024-03-06T23:24:16Z |
| format | Journal article |
| id | oxford-uuid:69d550dc-e889-4afa-80e2-68a3487849b8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:24:16Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:69d550dc-e889-4afa-80e2-68a3487849b82022-03-26T18:53:27ZAberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:69d550dc-e889-4afa-80e2-68a3487849b8EnglishSymplectic Elements at Oxford2009Lawson, VMaurice, DSilk, JCerundolo, VWeston, KThe transcription factors mediating the development of CD1d-restricted invariant NKT (iNKT) cells remain incompletely described. Here, we show that loss of the AP-1 transcription factor Fra-2 causes a marked increase in the number of both thymic and peripheral iNKT cells, without affecting the development of other T-lineage cells. The defect is cell-autonomous and is evident in the earliest iNKT precursors. We find that iNKT cells expressing the lower affinity TCRVbeta8 are proportionally overrepresented in the absence of Fra-2, indicating altered selection of iNKT cells. There is also widespread dysregulation of AP-1-directed gene expression. In the periphery, mature Fra-2-deficient iNKT cells are able to participate in an immune response, but they have an altered response to Ag, showing increased expansion and producing increased amounts of IL-2 and IL-4 compared with their wild-type counterparts. Unusually, naive Fra-2-deficient T cells also rapidly produce IL-2 and IL-4 upon activation. Taken together, these data define Fra-2 as necessary for regulation of normal iNKT cell development and function, and they demonstrate the central role played by the AP-1 family in this lineage. |
| spellingShingle | Lawson, V Maurice, D Silk, J Cerundolo, V Weston, K Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2. |
| title | Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2. |
| title_full | Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2. |
| title_fullStr | Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2. |
| title_full_unstemmed | Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2. |
| title_short | Aberrant selection and function of invariant NKT cells in the absence of AP-1 transcription factor Fra-2. |
| title_sort | aberrant selection and function of invariant nkt cells in the absence of ap 1 transcription factor fra 2 |
| work_keys_str_mv | AT lawsonv aberrantselectionandfunctionofinvariantnktcellsintheabsenceofap1transcriptionfactorfra2 AT mauriced aberrantselectionandfunctionofinvariantnktcellsintheabsenceofap1transcriptionfactorfra2 AT silkj aberrantselectionandfunctionofinvariantnktcellsintheabsenceofap1transcriptionfactorfra2 AT cerundolov aberrantselectionandfunctionofinvariantnktcellsintheabsenceofap1transcriptionfactorfra2 AT westonk aberrantselectionandfunctionofinvariantnktcellsintheabsenceofap1transcriptionfactorfra2 |