Azuz-Lieberman Niva, Markel Gal, Mizrahi Sa'ar, Gazit Roi, Hanna Jacob, Achdout Hagit, Gruda Raizy, Katz Gil, Arnon Tal I, Battat Shosh, Zamir Ehud, Adawi Muhammed, Mader Reuven, Mandelboim Ofer
The Lautenberg Center for General and Tumor Immunology, The Hebrew University, Hadassah Medical School, Jerusalem, 91120, Israel.
Int Immunol. 2005 Jul;17(7):837-45. doi: 10.1093/intimm/dxh270. Epub 2005 Jun 3.
A role for NK cells in the regulation of autoimmunity has been demonstrated. Since there is a strong association between Ankylosing Spondylitis (AS) and HLA-B27, which is specifically recognized by the NK-inhibitory receptor KIR3DL1, this study evaluated the potential involvement of NK cells in AS. We studied 19 AS patients and 22 healthy volunteer donors and assessed the percentage, activity and receptor expression of peripheral blood NK cells. We also evaluated candidate-inflammatory mediators in sera. We found that AS patients have significantly higher percentages of NK cells. However, we found no differences between the ability of NK cells derived from AS and healthy controls to recognize target cells expressing HLA-B27. Remarkably, we observed that the NK-inhibitory receptor CEACAM1 (carcino-embryonic antigen-cell adhesion molecule) is highly expressed among AS-derived NK cells. Furthermore, engagement of CEACAM1 inhibited NK activity in these patients. Finally, we demonstrated that CEACAM1 expression is induced by IL-8 and SDF-1 (stromal cell derived factor), both of which are present in high levels in the sera of AS patients. These results may indicate that NK cells and CEACAM1 play a role in AS pathogenesis and implicate chemokines in the mechanism of CEACAM1 expression.
自然杀伤细胞(NK细胞)在自身免疫调节中的作用已得到证实。由于强直性脊柱炎(AS)与NK抑制性受体KIR3DL1特异性识别的HLA - B27之间存在强关联,本研究评估了NK细胞在AS中的潜在作用。我们研究了19例AS患者和22名健康志愿者捐赠者,并评估了外周血NK细胞的百分比、活性和受体表达。我们还评估了血清中的候选炎症介质。我们发现AS患者的NK细胞百分比显著更高。然而,我们发现来自AS患者和健康对照的NK细胞识别表达HLA - B27的靶细胞的能力没有差异。值得注意的是,我们观察到NK抑制性受体癌胚抗原细胞粘附分子1(CEACAM1)在源自AS患者的NK细胞中高表达。此外,CEACAM1的结合抑制了这些患者的NK活性。最后,我们证明CEACAM1的表达是由白细胞介素 - 8(IL - 8)和基质细胞衍生因子1(SDF - 1)诱导的,这两种因子在AS患者血清中均高水平存在。这些结果可能表明NK细胞和CEACAM1在AS发病机制中起作用,并暗示趋化因子参与CEACAM1表达的机制。