| Autor: |
Bunting MD; Chemokine Biology Laboratory, School of Molecular and Biomedical Science, University of Adelaide and Centre for Molecular Pathology, Adelaide, South Australia, Australia., Comerford I, Seach N, Hammett MV, Asquith DL, Körner H, Boyd RL, Nibbs RJ, McColl SR |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2013 Jan 03; Vol. 121 (1), pp. 118-28. Date of Electronic Publication: 2012 Nov 14. |
| DOI: |
10.1182/blood-2012-06-434886 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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