Bunting, M.D., Comerford, I., Seach, N., Hammett, M. V., Asquith, D.L., Korner, H., Boyd, R. L., Nibbs, R.J.B. and McColl, S. R. (2013) CCX-CKR deficiency alters thymic stroma impairing thymocyte development and promoting autoimmunity. Blood, 121(1), pp. 118-128. (doi: 10.1182/blood-2012-06-434886)
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Abstract
The atypical chemokine receptor CCX-CKR regulates bioavailability of CCL19, CCL21, and CCL25, homeostatic chemokines that play crucial roles in thymic lymphopoiesis. Deletion of CCX-CKR results in accelerated experimental autoimmunity induced by immunization. Here we show that CCX-CKR deletion also increases incidence of a spontaneous Sjögren's syndrome-like pathology, characterized by lymphocytic infiltrates in salivary glands and liver of CCX-CKR−/− mice, suggestive of a defect in self-tolerance when CCX-CKR is deleted. This prompted detailed examination of the thymus in CCX-CKR−/− mice. Negatively selected mature SP cells were less abundant in CCX-CKR−/− thymi, yet expansion of both DP and immature SP cells was apparent. Deletion of CCX-CKR also profoundly reduced proportions of DN3 thymocyte precursors and caused DN2 cells to accumulate within the medulla. These effects are likely driven by alterations in thymic stroma as CCX-CKR−/− mice have fewer cTECs per thymocyte, and cTECs express the highest level of CCX-CKR in the thymus. A profound decrease in CCL25 within the thymic cortex was observed in CCX-CKR−/− thymi, likely accounting for their defects in thymocyte distribution and frequency. These findings identify a novel role for CCX-CKR in regulating cTEC biology, which promotes optimal thymocyte development and selection important for self-tolerant adaptive immunity.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Asquith, Dr Darren and Nibbs, Professor Rob |
| Authors: | Bunting, M.D., Comerford, I., Seach, N., Hammett, M. V., Asquith, D.L., Korner, H., Boyd, R. L., Nibbs, R.J.B., and McColl, S. R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Blood |
| ISSN: | 0006-4971 |
| ISSN (Online): | 1528-0020 |
| Published Online: | 14 November 2012 |
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