Differential regulation of CCL21 in lymphoid/nonlymphoid tissues for effectively attracting T cells to peripheral tissues.
Differential regulation of CCL21 in lymphoid/nonlymphoid tissues for effectively attracting T cells to peripheral tissues.
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DOI：
10.1172/jci19188
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发表时间：
2003-11
期刊：
影响因子：
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通讯作者：
J. Lo;R. Chin;Youjin Lee;Hyung-Sik Kang;Yang Wang;J. Weinstock;T. Banks;C. Ware;G. Franzoso;yang-xin fu
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文献类型：
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作者：
J. Lo;R. Chin;Youjin Lee;Hyung-Sik Kang;Yang Wang;J. Weinstock;T. Banks;C. Ware;G. Franzoso;yang-xin fu
CC趋化因子配体21（CCL 21）/次级淋巴样趋化因子（SLC）是CC趋化因子受体7（CCR 7）的配体，已被证明在免疫细胞向淋巴组织的归巢和定位中起重要作用，但其在非淋巴组织中的作用在很大程度上尚不清楚。在这里，我们提供的证据表明，CCL 21在淋巴组织和非淋巴组织的差异调节，分别由光敏素依赖（LT依赖）和非依赖机制。这种差异调节是由于LT和非经典NF-κ B途径对CCL 21-Ser/CCL 21 a而不是CCL 21-Leu/CCL 21 b基因的选择性调节。这种不依赖于LT或淋巴细胞的替代途径导致非淋巴组织中CCL 21的组成性表达，对于T淋巴细胞向外周效应位点的初始募集至关重要。CCL 21表达随后在气道激发后以LT依赖性方式进一步增强，潜在地促进正反馈回路以吸引额外的CCR 7+效应细胞。这些研究结果建立了一个重要的作用，CCL 21在招募效应T细胞到外周组织，并建议LT依赖性和非依赖性的调节CCL 21在平衡淋巴组织和非淋巴组织之间的中枢和外周免疫反应中发挥作用。
CC chemokine ligand 21 (CCL21)/secondary lymphoid chemokine (SLC), a ligand for CC chemokine receptor 7 (CCR7), has been demonstrated to play a vital role in the homing and localization of immune cells to lymphoid tissues, but its role in nonlymphoid tissues largely remains undefined. Here, we provide evidence that CCL21 in lymphoid and nonlymphoid tissues is differentially regulated by lymphotoxin-dependent (LT-dependent) and -independent mechanisms, respectively. This differential regulation is due to the selective regulation of the CCL21-Ser/CCL21a but not the CCL21-Leu/CCL21b gene by the LT and noncanonical NF-kappaB pathways. This alternate pathway, not dependent on LT or lymphocytes, leading to constitutive expression of CCL21 in nonlymphoid tissues, is critical for the initial recruitment of T lymphocytes to peripheral effector sites. CCL21 expression is subsequently further enhanced in a LT-dependent fashion following airway challenge, potentially facilitating a positive feedback loop to attract additional CCR7+ effector cells. These findings establish an essential role for CCL21 in the recruitment of effector T cells to peripheral tissues and suggest that LT-dependent and -independent regulation of CCL21 plays a role in balancing the central and peripheral immune responses between lymphoid and nonlymphoid tissues.