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. 2023 Apr;27(4):309-320.
doi: 10.1007/s10157-022-02307-9. Epub 2023 Jan 7.

HLA class II antibody activation of endothelial cells induces M2 macrophage differentiation in peripheral blood

Yingcong Guo #  1 , Bingxuan Zheng #  1 , Puxun Tian  1   2 , Jin Zheng  1   2 , Yang Li  1   2 , Xiaoming Ding  1   2 , Wujun Xue  1   2 , Chenguang Ding  3   4
Affiliations

HLA class II antibody activation of endothelial cells induces M2 macrophage differentiation in peripheral blood

Yingcong Guo et al. Clin Exp Nephrol. 2023 Apr.

Abstract

Background: Donor-specific human leukocyte antigen (HLA) class II antibodies (HLA-II Abs) combined with allogeneic endothelial cells (ECs) mediate high-risk rejection in kidney transplant patients. Macrophage accumulation is a significant histological feature of antibody-mediated rejection (AMR) in kidney transplant patients. Here, we further investigated the effect of HLA-II Abs on macrophage phenotypes to provide theoretical basis for clinical treatment of AMR.

Methods: We prepared an experimental model containing HLA-II Ab-stimulated microvascular ECs and peripheral blood mononuclear cells (PBMCs) co-culture and explored the potential relationship of HLA-II Ab, ECs activation, and macrophage differentiation. Immune phenotype of macrophage subsets was analyzed and quantified by flow cytometry. HLA-II Ab activation of ECs induces M2 macrophage differentiation signal pathways which were investigated by qPCR and western blotting.

Results: The stimulation of ECs by F(ab')2 fragment of HLA-II Abs led to phosphorylation of PI3K, Akt, and mTOR, which mediated IL-10, ICAM-1, VCAM-1 secretion. The enhanced ICAM-1 and IL-10 promoted the migration of PBMCs and their differentiation into CD68+ and CD163+ (M2-type) macrophages, respectively, but not CD86+ macrophages.

Conclusion: These findings revealed the PI3K/Akt/mTOR signal pathways activated by HLA-II Abs in ECs and the immune regulation ability of HLA-II Abs to induce PBMC differentiation.

Keywords: Antibody-mediated rejection; Endothelial cells; HLA-II Abs; M2 macrophage; PBMCs.

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