Abstract
Netrin-1, a known axon guidance molecule, being a secreted laminin-related molecule, has been suggested to be involved in multiple physiological and pathological conditions, such as organogenesis, angiogenesis, tumorigenesis, and inflammation-mediated tissue injury. However, its function in thymocyte development is still unknown. Here, we demonstrate that Netrin-1 is expressed in mouse thymus tissue and is primarily expressed in thymic stromal cells, and the expression of Netrin-1 in thymocytes can be induced by anti-CD3 antibody or IL-7 treatment. Importantly, Netrin-1 mediates the adhesion of thymocytes, and this effect is comparable to or greater than that of fibronectin. Furthermore, Netrin-1 specifically promotes the chemotaxis of CXCL12. These suggest that Netrin-1 may play an important role in thymocyte development.
Highlights
The thymus is the site for T-cell development [1]
In an attempt to identify whether Netrin-1 plays a significant role in thymocyte development, first we investigated whether Netrin-1 or its cognate receptors were expressed in the thymus
By reverse transcription (RT) PCR, it was shown that Netrin-1 was expressed by freshly isolated thymic stromal cells (TSC) as well as multiple thymic epithelial cell lines (Figure 1(a))
Summary
The thymus is the site for T-cell development [1]. Bonemarrow-derived progenitors enter the thymus and follow a well-defined differentiation program to complete their maturation [2]. During this process, developmental thymocytes undergo oriented migration throughout the various anatomical niches within the thymic lobules. The main chemokine expressed in the thymus is CXCL12 (SDF-1α), which is secreted by thymic epithelial cells (TEC) located in the subcapsular and medullar regions. The corresponding specific receptor CXCR4 is mainly expressed in these stages of thymocyte development. Thymus-specific deletion of CXCR4 in vivo led to failed cortical localization of these progenitors, together with arrest of developmental process [10, 11]. The chemokines CCL25 (TECK) and CCL22 (macrophagederived chemokine) mediate chemotaxis of immature thymocytes, whereas CCL19 and CCL21 mainly exert chemotactic effects on CD4SP or CD8 SP thymocytes [12, 13]
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