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The mechanisms that control such oscillatory migration involves transient S1PR1 desensitization (for migration from the marginal zone into the follicles), followed by S1PR1 resensitization (for migration back to the marginal zone; Mehta et al., 2014). Moreover, the marginal zone is also permanently planted with many DCs, which, after digestion and reactivation with antigens, can express CCR7. Through the movement orbit of T cells, they could enter the T-cell zone and reactivate the antigen-specific T cells (Turley et al., 2010). Just as mentioned before, except some kinds of cells (e.g., T cells, B cells, and DCs), other cells will flow along the blood stream into the red pulp. Myeloid-derived suppressor cells (MDSCs) which express CCR2 could be attracted by CCL2 and retain in the red pulp. Besides, bone marrow hematopoietic stem/progenitor cells (HSPCs) also could retain in the red pulp by vascular cell adhesion molecule 1 (VCAM-1)+ macrophages, which use the adhesion molecule VCAM-1 to retain HSPCs through its receptor �C very late antigen 4 (VLA-4; Bronte and Pittet, 2013). In certain condition, a large amount of MDSCs or HSPCs could accumulate in the red pulp and influence the immune response. In the end, rest of the cells would flow out of the spleen along the blood stream (Figure ?Figure1C1C). Regulation of Chemokine Secretion The expressions of CCL21 and CCL19 by FRCs in the splenic T cell zone and LNs facilitate the effective interaction between DCs and T cells (Luther et al., 2011). The secretion of these chemokines in SLOs is not constant, but can be regulated by RRAD different molecules. Firstly, previous research shows that the mesenchymal cells of SLOs require continuous signals from many molecules, so as to maintain their secretion of CCL21 and 19. The most-studied molecules are the tumor necrosis factor (TNF) family members. For example: LTs and TNFs are among such signaling molecules (Klaus et al., 1980; Schneider et al., 2004; Zhao et al., 2015). The deletion of these factors will induce the down-regulation of CCL21 and CCL19. However, the redundancy in TNF/LT ligand-receptor interactions complicates the understanding about the distinct contribution of particular ligand to the complex phenotype of TNF/LT-deficient mice (Tumanov et al., 2003; Zhao et al., 2014). In addition, these maintaining factors are mainly secreted by lymphocytes (Sixt et al., 2005; Zhao et al., 2014). As reported, the deletion of T cells will also lead to the significantly down-regulated secretory volumes of CCL19 and CCL21, and the expression levels of these chemokines can be recovered after the transfusion of T cells. Even the maintaining effects of these factors have not changed, some molecules also could directly down-regulate the expressions of CCL21 and CCL19.