| First Author | Bunting MD | Year | 2013 |
| Journal | Blood | Volume | 121 |
| Issue | 1 | Pages | 118-28 |
| PubMed ID | 23152546 | Mgi Jnum | J:193138 |
| Mgi Id | MGI:5467695 | Doi | 10.1182/blood-2012-06-434886 |
| Citation | Bunting MD, et al. (2013) CCX-CKR deficiency alters thymic stroma impairing thymocyte development and promoting autoimmunity. Blood 121(1):118-28 |
| abstractText | 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 Sjogren'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. |
