Lupus Heterogeneity Highlighted With Single-Cell Transcriptomes

Lupus erythematosus (LE) is a severe autoimmune disease characterized by the presence of many abnormal immune cells and a large number of autoantibodies and immune complexes, all of which lead to damage to multiple organs, such as the skin, kidney, and brain.

Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are both types of lupus, yet the characteristics, and differences between them are not fully understood. Cutaneous lupus erythematosus (CLE), which mainly presents as dermatological injuries and does not involve systemic damage. Discoid lupus erythematosus (DLE) accounts for >80% of cases of CLE and is the most common type of CLE.

A team of Dermatologists at the Central South University (Changsha, China) and their colleagues collected 23 skin biopsy samples from eight DLE patients with an average age of 40.4 ± 11.0 years, 10 SLE patients with an average age of 41.4 ± 12.3 years and five healthy controls (HCs) with an average age of 32.4 ± 6.0 years, were collected. The scientists performed single cell RNA-Seq (scRNA-seq) on 14 epidermal single-cell suspensions (four HCs, five DLE, and five SLE samples) and 16 dermal single-cell suspensions (four HCs, five DLE, and seven SLE) by the 10× Genomics Chromium system (Pleasanton, CA, USA).

The investigators reported that they found significantly higher proportions of T cells, B cells and NK cells in DLE than in SLE. Expanded CCL20+ keratinocyte, CXCL1+ fibroblast, ISGhiCD4/CD8 T cell, ISGhi plasma cell, pDC, and NK subclusters were identified in DLE and SLE compared to HC. In addition, they observed higher cell communication scores between cell types such as fibroblasts and macrophage/dendritic cells in cutaneous lesions of DLE and SLE compared to HC. The proportions of T cells, B cells, Macro/DC, and NK cells were 29.5%, 1.7%, 10.2%, and 3.5%, respectively, in the epidermis of DLE patients, and 31.2%, 0.4%, 8.6%, and 1.9%, respectively, in the epidermis of SLE patients, which were higher than those in the epidermis of HC. In the dermis, the receptors of CCL19 (CCR7, CCR2, and CXCR3), CXCL12 (CXCR4), FAM3C (CLEX2D), and TNFSF13B (CD40) in fibroblasts showed the highest expression in B, Macro/DCs, NK, and T cells in the DLE group among the three sample groups.

The authors concluded that their findings provide much information about DLE- and SLE-specific cellular and molecular signatures in cutaneous lesions compared to that of healthy controls. They described in detail the similarities and differences in cell compositions between DLE and SLE, which will help understand the pathogenesis of DLE and SLE and develop novel and precise therapeutic targets for lupus erythematosus. The study was published on December 5 2022 in the journal Nature Communications.

Related Links:
Central South University
10× Genomics