CXCR4 is dispensable for T cell egress from chronically inflamed skin via the afferent lymph.
CXCR4 is dispensable for T cell egress from chronically inflamed skin via the afferent lymph.
复制标题
DOI：
10.1371/journal.pone.0095626
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Debes GF
中科院分区：
文献类型：
--
作者：
Geherin SA;Wilson RP;Jennrich S;Debes GF
T细胞通过淋巴外组织的再循环对于免疫监视、宿主防御和炎症是必不可少的。在这个过程中，T细胞从血液进入组织，随后通过传入淋巴离开。在没有炎症的情况下，T细胞需要CCR 7表达以从皮肤或肺中排出，这与淋巴内皮上CCR 7配体CCL 21的组成型表达一致。然而，在慢性炎症期间，替代性化学引诱物发挥作用，允许Ccr 7缺陷型（Ccr 7 −/−）T细胞有效地从受影响的皮肤中排出。由于T细胞从发炎部位流出是炎症反应的潜在控制点，我们的目的是使用小鼠和绵羊模型确定替代T细胞出口受体。我们发现，从慢性炎症皮肤中排出的CCR 7+和CCR 7- T细胞对CXCR 4配体CXCL 12高度应答，CXCL 12在炎症部位的炎症中诱导。基于这些发现，我们假设CXCR 4介导T细胞从发炎皮肤中排出。然而，CXCR 4的药理学抑制并不影响野生型或Ccr 7 −/− CD 4和CD 8 T细胞过继转移到慢性炎症皮肤后的组织流出。同样，过继转移的Cxcr 4 −/− Ccr 7 −/−和Ccr 7 −/− T细胞从发炎的皮肤中同样良好地排出。基于这些数据，我们得出结论，虽然CXCR 4可能对进入传入神经系统的其他细胞类型起重要作用，但它对T细胞从慢性炎症皮肤中的排出是不利的。
T cell recirculation through extralymphoid tissues is essential to immune surveillance, host defense and inflammation. In this process, T cells enter the tissue from the blood and subsequently leave via the afferent lymph. In the absence of inflammation, T cells require CCR7 expression to egress from the skin or lung, which is consistent with the constitutive expression of the CCR7 ligand CCL21 on lymphatic endothelium. However, during chronic inflammation alternative chemoattractants come into play, allowing Ccr7-deficient (Ccr7−/−) T cells to egress efficiently from affected skin. As T cell egress from inflamed sites is a potential control point of the inflammatory response, we aimed to determine alternative T cell exit receptors using a mouse and a sheep model. We show that CCR7+ and CCR7– T cells exiting from the chronically inflamed skin were highly responsive to the CXCR4 ligand CXCL12, which was induced in the lymphatics in the inflamed site. Based on these findings, we hypothesized that CXCR4 mediates T cell egress from inflamed skin. However, pharmacological inhibition of CXCR4 did not affect the tissue egress of wildtype or Ccr7−/− CD4 and CD8 T cells after adoptive transfer into chronically inflamed skin. Similarly, adoptively transferred Cxcr4−/− Ccr7−/− and Ccr7−/− T cells egressed from the inflamed skin equally well. Based on these data, we conclude that, while CXCR4 might play an essential role for other cell types that enter the afferent lymphatics, it is dispensable for T cell egress from the chronically inflamed skin.
登录
查看更多内容
DOI：
10.1073/pnas.86.17.6734
发表时间：
1989-09-01
影响因子：
11.1
作者：
BIRKELAND, ML;JOHNSON, P;PURE, E
通讯作者：
PURE, E
DOI：
10.4049/jimmunol.1102639
发表时间：
2012-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Geherin SA;Fintushel SR;Lee MH;Wilson RP;Patel RT;Alt C;Young AJ;Hay JB;Debes GF
通讯作者：
Debes GF
影响因子：
64.5
作者：
Förster, R;Schubel, A;Lipp, M
通讯作者：
Lipp, M
影响因子：
4.4
作者：
Infantino, S;Moepps, B;Thelen, M
通讯作者：
Thelen, M
影响因子：
7.3
作者：
BRIDGER, GJ;SKERLJ, RT;DECLERCQ, E
通讯作者：
DECLERCQ, E