CXCR3 ligands contribute to Th1-induced inflammation but not to homing of Th1 cells into the lung.

CXCR3 ligands contribute to Th1-induced inflammation but not to homing of Th1 cells into the lung.
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DOI:
10.1080/01902140802221987
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发表时间:
2008-09
影响因子:
1.7
通讯作者:
Clark JG
Clark JG
中科院分区:
医学4区
文献类型:
--
作者:
Manicone AM;Burkhart KM;Lu B;Clark JG

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. Th 1细胞与许多肺部炎症性疾病有关,同种异体反应性Th 1细胞的过继转移介导小鼠的肺损伤和炎症。在对Th 1介导的免疫损伤的应答中,CXCR 3配体IP 10和IP 14被显著诱导。因为Th 1细胞表达高水平的CXCR 3,它们的募集和活性可能受到CXCR 3配体的影响。.为了研究CXCR 3配体的作用,我们通过两种方法抑制CXCR 3-配体相互作用:1)CXCR 3配体IP 10和IP 10的抗体消融,以及2)使用cxcr 3 −/−小鼠。.抗体中和IP 10和CD 4+减少Th 1细胞介导的肺部炎症,但不改变Th 1细胞流入肺。相反,宿主细胞上CXCR 3的缺乏对Th 1细胞流入或急性炎症没有影响。在体外,消融内源性IP 10和IL 10抑制抗原介导的Th 1细胞增殖。.这些结果表明,同种异体反应性Th 1细胞流入肺不需要CXCR 3配体,但这些趋化因子确实影响Th 1细胞增殖和受影响组织内的活性。其他CXCR 3+白细胞不会导致急性同种免疫损伤。
. Th1 cells are implicated in numerous pulmonary inflammatory disorders, and adoptive transfer of alloreactive Th1 cells mediates lung injury and inflammation in mice. In response to Th1-mediated immune injury, CXCR3 ligands IP10 and MIG are markedly induced. Because Th1 cells express high levels of CXCR3, their recruitment and activity may be influenced by CXCR3 ligands. . To examine the role of CXCR3 ligands, we inhibited CXCR3-ligand interaction by two approaches: 1) antibody ablation of CXCR3 ligands IP10 and MIG, and 2) use of cxcr3−/− mice. . Antibody neutralization of IP10 and MIG reduced Th1-cell mediated lung inflammation but did not alter Th1 cell influx in the lung. In contrast, a lack of CXCR3 on host cells had no effect on Th1 cells influx or acute inflammation. In vitro, ablation of endogenous IP10 and MIG inhibited antigen-mediated Th1 cell proliferation. . These results suggest that the influx of alloreactive Th1 cells into the lung does not require CXCR3 ligands, but that these chemokines do affect Th1 cell proliferation and activity within the affected tissue. Other CXCR3+ leukocytes do not contribute to acute alloimmune injury.
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