Investigation of the expression and biological response of the IL-1Rrp2 receptor in human cells
Dysregulated IL-1 activity has been implicated in the pathogenesis of several acute and chronic inflammatory as well as autoimmune diseases. Genomic analysis has identified additional IL-1 family members and also expanded the IL-1 receptor family. To date, there are eleven IL-1 family members and ni...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2012
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| Online Access: | https://eprints.nottingham.ac.uk/12988/ |
| _version_ | 1848791623883816960 |
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| author | Mutamba, Shilla |
| author_facet | Mutamba, Shilla |
| author_sort | Mutamba, Shilla |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Dysregulated IL-1 activity has been implicated in the pathogenesis of several acute and chronic inflammatory as well as autoimmune diseases. Genomic analysis has identified additional IL-1 family members and also expanded the IL-1 receptor family. To date, there are eleven IL-1 family members and nine IL-1 receptor family members. Information regarding the biological activity and immunological role of the newer IL-1 family members is still very limited. The novel IL-1 cytokines, IL-1F6, IL-1F8 and IL-1F9 (recently renamed IL-36α, IL-36β and IL-36γ respectively) have been shown to signal via IL-1 receptor related protein 2 (IL-1Rrp2, recently renamed IL-36R). The main aims of this study were: (i) to investigate the expression of IL-1Rrp2 by human myelomonocytic and non-myelomonocytic immune cells as well as other human cells, (ii) to determine the possible function of IL-1Rrp2 and (iii) to determine the effect of IL-1Rrp2 expression on T lymphocytes. Results reported in this thesis indicate that among human myelomonocytic cells, constitutive IL-1Rrp2 expression is unique to dendritic cells (DCs). IL-1Rrp2 was expressed by monocyte- derived DCs (MDDCs) and plasmacytoid DCs (pDCs) but not by peripheral blood type 1 or type 2 myeloid DCs (mDC1 or mDC2). IL-1Rrp2 expression was regulated in response to both classical (IL-1β) and novel IL-1 cytokines (IL-1F8 and IL-1F9). Similarly to IL-1β and bacterial LPS, novel IL-1 cytokines mediated DC maturation as shown by DC phenotypic changes (e.g. upregulation of HLA-DR expression and decreased CD1a expression following culture of DCs with IL-1F8) and cytokine production. Among non-myelomonocytic cells, constitutive IL-1Rrp2 expression was observed in lamina propria tissue, T lymphocytes, NCI/ADR-RES cells and HT 29 cells. IL-1F8-matured human DCs were fully functional as they induced proliferation of IFN-γ-producing TH1 subsets. Results suggest that novel IL-1 cytokines play a role in inflammatory responses involving human DCs, with possible implications for inflammatory disease. |
| first_indexed | 2025-11-14T18:31:28Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-12988 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T18:31:28Z |
| publishDate | 2012 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-129882025-02-28T11:22:29Z https://eprints.nottingham.ac.uk/12988/ Investigation of the expression and biological response of the IL-1Rrp2 receptor in human cells Mutamba, Shilla Dysregulated IL-1 activity has been implicated in the pathogenesis of several acute and chronic inflammatory as well as autoimmune diseases. Genomic analysis has identified additional IL-1 family members and also expanded the IL-1 receptor family. To date, there are eleven IL-1 family members and nine IL-1 receptor family members. Information regarding the biological activity and immunological role of the newer IL-1 family members is still very limited. The novel IL-1 cytokines, IL-1F6, IL-1F8 and IL-1F9 (recently renamed IL-36α, IL-36β and IL-36γ respectively) have been shown to signal via IL-1 receptor related protein 2 (IL-1Rrp2, recently renamed IL-36R). The main aims of this study were: (i) to investigate the expression of IL-1Rrp2 by human myelomonocytic and non-myelomonocytic immune cells as well as other human cells, (ii) to determine the possible function of IL-1Rrp2 and (iii) to determine the effect of IL-1Rrp2 expression on T lymphocytes. Results reported in this thesis indicate that among human myelomonocytic cells, constitutive IL-1Rrp2 expression is unique to dendritic cells (DCs). IL-1Rrp2 was expressed by monocyte- derived DCs (MDDCs) and plasmacytoid DCs (pDCs) but not by peripheral blood type 1 or type 2 myeloid DCs (mDC1 or mDC2). IL-1Rrp2 expression was regulated in response to both classical (IL-1β) and novel IL-1 cytokines (IL-1F8 and IL-1F9). Similarly to IL-1β and bacterial LPS, novel IL-1 cytokines mediated DC maturation as shown by DC phenotypic changes (e.g. upregulation of HLA-DR expression and decreased CD1a expression following culture of DCs with IL-1F8) and cytokine production. Among non-myelomonocytic cells, constitutive IL-1Rrp2 expression was observed in lamina propria tissue, T lymphocytes, NCI/ADR-RES cells and HT 29 cells. IL-1F8-matured human DCs were fully functional as they induced proliferation of IFN-γ-producing TH1 subsets. Results suggest that novel IL-1 cytokines play a role in inflammatory responses involving human DCs, with possible implications for inflammatory disease. 2012-12-12 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/12988/1/Shilla_Mutamba_POST-VIVA_PhD_Thesis_FINAL_pdf.pdf Mutamba, Shilla (2012) Investigation of the expression and biological response of the IL-1Rrp2 receptor in human cells. PhD thesis, University of Nottingham. IL-1 IL-1Rrp2 receptor IL-36R IL-1F6 IL-1F8 IL-1F9 IL-36 alpha IL-36 beta IL-36 gamma dendritic cells MDDC pDCs plasmacytoid monocyte derived dendritic cells novel IL-1 |
| spellingShingle | IL-1 IL-1Rrp2 receptor IL-36R IL-1F6 IL-1F8 IL-1F9 IL-36 alpha IL-36 beta IL-36 gamma dendritic cells MDDC pDCs plasmacytoid monocyte derived dendritic cells novel IL-1 Mutamba, Shilla Investigation of the expression and biological response of the IL-1Rrp2 receptor in human cells |
| title | Investigation of the expression and biological response
of the IL-1Rrp2 receptor in human cells |
| title_full | Investigation of the expression and biological response
of the IL-1Rrp2 receptor in human cells |
| title_fullStr | Investigation of the expression and biological response
of the IL-1Rrp2 receptor in human cells |
| title_full_unstemmed | Investigation of the expression and biological response
of the IL-1Rrp2 receptor in human cells |
| title_short | Investigation of the expression and biological response
of the IL-1Rrp2 receptor in human cells |
| title_sort | investigation of the expression and biological response
of the il-1rrp2 receptor in human cells |
| topic | IL-1 IL-1Rrp2 receptor IL-36R IL-1F6 IL-1F8 IL-1F9 IL-36 alpha IL-36 beta IL-36 gamma dendritic cells MDDC pDCs plasmacytoid monocyte derived dendritic cells novel IL-1 |
| url | https://eprints.nottingham.ac.uk/12988/ |