Monocyte profile and function in sarcoidosis
<p>Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology. The immune pathology is characterised by dysregulated T cell (T<sub>H</sub>1) activity, macrophage activation and granuloma formation, resulting in systemic inflammation, and organ dysfunction. I hypothesis...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
2014
|
| _version_ | 1817932664175329280 |
|---|---|
| author | Crawshaw, A Dr Anjali Priya Crawshaw |
| author2 | Ho, L |
| author_facet | Ho, L Crawshaw, A Dr Anjali Priya Crawshaw |
| author_sort | Crawshaw, A |
| collection | OXFORD |
| description | <p>Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology. The immune pathology is characterised by dysregulated T cell (T<sub>H</sub>1) activity, macrophage activation and granuloma formation, resulting in systemic inflammation, and organ dysfunction. I hypothesised that, as the systemic precursor to the macrophage, altered monocyte activity in sarcoidosis may contribute to the early immune pathology of the disease. In this thesis, I examined their phenotype, four key monocytic functions: cytokine production, suppression of T cell proliferation, phagocytosis and fusion (as a precursor to granulomagenesis); and their gene expression profile compared to monocytes from healthy controls.</p> <p>My data show that the expanded monocyte compartment comprise a greater proportion of the inflammatory (CD14<sup>++</sup>CD16<sup>+</sup>) and patrolling (CD14<sup>+</sup>CD16<sup>++</sup>) subsets, increased TNFα and IL-12 and decreased IL-10 and IL-4 production in sarcoidosis compared with healthy controls. The IL-10 deficit renders the monocytes less able to regulate T cell proliferation or their own fusion to multinucleate giant cells, potentially contributing to T cell expansion and granuloma formation respectively. Additionally, sarcoidosis monocytes are less able to phagocytose inert material. I also showed that previously reported deficiency in invariant NKT cells and low serum vitamin D levels in sarcoidosis may be linked to reduced IL-10 production by monocytes. Vitamin D treatment in vitro restored most of these deficiencies and provides a potential therapeutic method for manipulating monocyte function and disease genesis in sarcoidosis.</p> |
| first_indexed | 2024-03-06T20:38:36Z |
| format | Thesis |
| id | oxford-uuid:3378bf46-a494-45a0-b68e-81b37c1dae49 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:41:30Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:3378bf46-a494-45a0-b68e-81b37c1dae492024-12-07T12:35:44ZMonocyte profile and function in sarcoidosisThesishttp://purl.org/coar/resource_type/c_db06uuid:3378bf46-a494-45a0-b68e-81b37c1dae49EnglishOxford University Research Archive - Valet2014Crawshaw, ADr Anjali Priya CrawshawHo, LMcMichael, A<p>Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology. The immune pathology is characterised by dysregulated T cell (T<sub>H</sub>1) activity, macrophage activation and granuloma formation, resulting in systemic inflammation, and organ dysfunction. I hypothesised that, as the systemic precursor to the macrophage, altered monocyte activity in sarcoidosis may contribute to the early immune pathology of the disease. In this thesis, I examined their phenotype, four key monocytic functions: cytokine production, suppression of T cell proliferation, phagocytosis and fusion (as a precursor to granulomagenesis); and their gene expression profile compared to monocytes from healthy controls.</p> <p>My data show that the expanded monocyte compartment comprise a greater proportion of the inflammatory (CD14<sup>++</sup>CD16<sup>+</sup>) and patrolling (CD14<sup>+</sup>CD16<sup>++</sup>) subsets, increased TNFα and IL-12 and decreased IL-10 and IL-4 production in sarcoidosis compared with healthy controls. The IL-10 deficit renders the monocytes less able to regulate T cell proliferation or their own fusion to multinucleate giant cells, potentially contributing to T cell expansion and granuloma formation respectively. Additionally, sarcoidosis monocytes are less able to phagocytose inert material. I also showed that previously reported deficiency in invariant NKT cells and low serum vitamin D levels in sarcoidosis may be linked to reduced IL-10 production by monocytes. Vitamin D treatment in vitro restored most of these deficiencies and provides a potential therapeutic method for manipulating monocyte function and disease genesis in sarcoidosis.</p> |
| spellingShingle | Crawshaw, A Dr Anjali Priya Crawshaw Monocyte profile and function in sarcoidosis |
| title | Monocyte profile and function in sarcoidosis |
| title_full | Monocyte profile and function in sarcoidosis |
| title_fullStr | Monocyte profile and function in sarcoidosis |
| title_full_unstemmed | Monocyte profile and function in sarcoidosis |
| title_short | Monocyte profile and function in sarcoidosis |
| title_sort | monocyte profile and function in sarcoidosis |
| work_keys_str_mv | AT crawshawa monocyteprofileandfunctioninsarcoidosis AT dranjalipriyacrawshaw monocyteprofileandfunctioninsarcoidosis |