Human CD141+ dendritic cells: A unique tolerogenic subset inducing immune tolerance in systemic lupus erythematosus patients

Abstract

Abstract Background Tolerogenic dendritic cells (DCs) are promising for cell‐based treatment for systemic lupus erythematosus (SLE). We previously showed that tolerogenic CD1c+ DCs play an important role in mesenchymal stem cell transplantation treatment of SLE. We further investigated the immunoregulatory effects of CD141+ DCs on lupus pathogenesis. Methods A total of 12 SLE patients and 12 age‐ and sex‐matched healthy subjects were included in the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2019 to January 2021. The percentage of peripheral blood CD141+ DCs and their functional expressions of costimulatory markers (CD40, CD80, CD83, and CD86) were compared between patients with SLE and healthy controls. Moreover, the tolerogenic properties of CD141+ and CD1c+ DCs were compared following stimulation with lipopolysaccharide (LPS) or SLE serum. Results Our research revealed that the presence of peripheral CD141+ DCs decreased in SLE patients compared with controls (1.03% ± 0.40% vs. 1.44% ± 0.36%, p < 0.05), which was negatively correlated with the SLE disease activity index score (R2 = 0.5547, p = 0.0055). Moreover, CD141+ DCs in patients with SLE exhibited distinct tolerogenic properties by decreasing the mean fluorescence intensity (MFI) of CD40, CD80, and CD86 when compared with controls (2447.00 ± 1386.14 vs. 11,357.25 ± 4581.05, p < 0.001; 1528.00 ± 876.61 vs. 14,181.42 ± 7599.33, p < 0.001; 17,409.42 ± 8180.98 vs. 33,614.25 ± 7408.69, p < 0.001). Furthermore, CD141+ DCs exhibited superior tolerogenicity when compared to CD1c+ DCs in SLE, by reducing MFI of CD86 (93,526.58 ± 51,763.00 vs. 169,552.00 ± 51,225.74, p < 0.01 by LPS stimulation; 107,837.40 ± 26,124.76 vs. 145,450.90 ± 50,436.69, p < 0.05 by SLE serum stimulation), and reducing production of tumor necrosis factor α (8.83% ± 3.51% vs. 13.94% ± 2.87%, p < 0.05 by LPS stimulation; 10.12% ± 2.34% vs. 14.39% ± 2.70%, p < 0.05 by SLE serum stimulation). Conclusions CD141+ DCs play a more significant role than the commonly studied CD1c+ DCs in ameliorating immune dysfunction and maintaining immune homeostasis in SLE. Our findings contribute to a better understanding of the immunoregulatory mechanisms underlying SLE and pave the way for novel therapeutic approaches targeting CD141+ DCs.

Keywords

• dendritic cells
• immune tolerance
• systemic lupus erythematosus