Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis.
Sarcoidosis is a multisystem granulomatous disorder characterized by marked T-cell expansion of T helper 1 (Th1) cells. The cause of T-cell overactivity is unknown. We hypothesized that interleukin-10 (IL-10) production by a yet undefined cell type might be defective, resulting in loss of regulation...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Wiley
2014
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| _version_ | 1797074395516108800 |
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| author | Crawshaw, A Kendrick, Y Mcmichael, A Ho, L |
| author_facet | Crawshaw, A Kendrick, Y Mcmichael, A Ho, L |
| author_sort | Crawshaw, A |
| collection | OXFORD |
| description | Sarcoidosis is a multisystem granulomatous disorder characterized by marked T-cell expansion of T helper 1 (Th1) cells. The cause of T-cell overactivity is unknown. We hypothesized that interleukin-10 (IL-10) production by a yet undefined cell type might be defective, resulting in loss of regulation of T-cell activity. Focusing on IL-10-producing monocytes, we first showed that monocytes isolated from the peripheral blood of corticosteroid-naïve sarcoidosis patients (n = 51) produced less IL-10 compared to controls, and were less able to suppress T-cell proliferation. In addition, monocytic IL-10 production correlated negatively with disease activity score. As invariant natural killer T (iNKT) cells are known to both interact with monocytes and be reduced in sarcoidosis patients, we then asked whether iNKT-specific defects might be responsible for this reduced IL-10 production. We found that greater numbers of circulating iNKT cells was associated with higher IL-10 production. Moreover, iNKT cells enhanced monocytic IL-10 production in vitro. Defective IL-10 production and T-cell suppression by sarcoidosis monocytes could be restored following their coculture with iNKT cells, in a CD1d- and cell contact-dependent process. We suggest that reduced iNKT-cell numbers in sarcoidosis may lead to impaired monocytic IL-10 production and unchecked T-cell expansion in sarcoidosis. These findings provide fresh insight into the mechanism of sarcoidosis disease, and interaction between iNKT cells and monocytes. |
| first_indexed | 2024-03-06T23:35:31Z |
| format | Journal article |
| id | oxford-uuid:6d85959d-5302-468b-b324-90430042b6c7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:35:31Z |
| publishDate | 2014 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:6d85959d-5302-468b-b324-90430042b6c72022-03-26T19:18:19ZAbnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6d85959d-5302-468b-b324-90430042b6c7EnglishSymplectic Elements at OxfordWiley2014Crawshaw, AKendrick, YMcmichael, AHo, LSarcoidosis is a multisystem granulomatous disorder characterized by marked T-cell expansion of T helper 1 (Th1) cells. The cause of T-cell overactivity is unknown. We hypothesized that interleukin-10 (IL-10) production by a yet undefined cell type might be defective, resulting in loss of regulation of T-cell activity. Focusing on IL-10-producing monocytes, we first showed that monocytes isolated from the peripheral blood of corticosteroid-naïve sarcoidosis patients (n = 51) produced less IL-10 compared to controls, and were less able to suppress T-cell proliferation. In addition, monocytic IL-10 production correlated negatively with disease activity score. As invariant natural killer T (iNKT) cells are known to both interact with monocytes and be reduced in sarcoidosis patients, we then asked whether iNKT-specific defects might be responsible for this reduced IL-10 production. We found that greater numbers of circulating iNKT cells was associated with higher IL-10 production. Moreover, iNKT cells enhanced monocytic IL-10 production in vitro. Defective IL-10 production and T-cell suppression by sarcoidosis monocytes could be restored following their coculture with iNKT cells, in a CD1d- and cell contact-dependent process. We suggest that reduced iNKT-cell numbers in sarcoidosis may lead to impaired monocytic IL-10 production and unchecked T-cell expansion in sarcoidosis. These findings provide fresh insight into the mechanism of sarcoidosis disease, and interaction between iNKT cells and monocytes. |
| spellingShingle | Crawshaw, A Kendrick, Y Mcmichael, A Ho, L Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis. |
| title | Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis. |
| title_full | Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis. |
| title_fullStr | Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis. |
| title_full_unstemmed | Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis. |
| title_short | Abnormalities in iNKT cells are associated with impaired ability of monocytes to produce IL-10 and suppress T-cell proliferation in sarcoidosis. |
| title_sort | abnormalities in inkt cells are associated with impaired ability of monocytes to produce il 10 and suppress t cell proliferation in sarcoidosis |
| work_keys_str_mv | AT crawshawa abnormalitiesininktcellsareassociatedwithimpairedabilityofmonocytestoproduceil10andsuppresstcellproliferationinsarcoidosis AT kendricky abnormalitiesininktcellsareassociatedwithimpairedabilityofmonocytestoproduceil10andsuppresstcellproliferationinsarcoidosis AT mcmichaela abnormalitiesininktcellsareassociatedwithimpairedabilityofmonocytestoproduceil10andsuppresstcellproliferationinsarcoidosis AT hol abnormalitiesininktcellsareassociatedwithimpairedabilityofmonocytestoproduceil10andsuppresstcellproliferationinsarcoidosis |