TNFRSF and the corresponding ligands involved in the activation of the alternative NF-κB pathway across various human tissues and cell types
| Ligand (gene) . | Tissue expression . | Cellular expression . | Receptor (gene) . | Tissue expression . | Cellular expression . | Reference . |
|---|---|---|---|---|---|---|
| CD40L or CD154 (CD40LG) | SLOs and thymus | Leukocytes: activated T cells (CD4+, CD8+, and γδ), NKT, MAIT, Tregs, also detected on NK cells, mast cells, basophils, and eosinophils | CD40 or TNFRSF5 (CD40) | SLOs and thymus | Leukocytes: B cells, dendritic cells, monocytes, and macrophages. Non-hematopoietic cells: epithelial cells (mTECs), follicular dendritic cells, endothelial cells, and fibroblasts | (11, 12) |
| LTα1β2 (LTA and LTB) | SLOs, thymus, and bone marrow | Leukocytes: activated B and T cells, NKT, MAIT, Tregs, and dendritic cells | LTβR or TNFRSF3 (LTBR) | SLOs, thymus, and bone marrow | Leukocytes: dendritic cells, monocytes, and macrophages. Non-hematopoietic cells: LN stromal cells (FRCs, including MRCsa), epithelial cells, endothelial cells, and mesenchymal cells | (12, 13, 14) |
| LIGHT (TNFSF14) | Broad, including bone marrow, SLOs, and liver | Leukocytes: T cells, NK cells, macrophages, monocytes, and dendritic cells | ||||
| LIGHT-R or HVEM (TNFRSF14) | Broad, including SLOs | B and T lymphocytes, NK cells, monocytes, macrophages, and dendritic cells | (12, 15) | |||
| RANKL (TNFSF11) | SLOs, bone marrow, bones, and thymus | Leukocytes: activated T and B cells and NK cells. Non-hematopoietic cells: osteoblasts, osteocytes, LN stromal cells (MRCsa), epithelial, and germ cells | RANK (TNFRSF11A) | Gastrointestinal tract, SLOs, and bones | Hematopoietic cells: osteoclasts, macrophages, dendritic cells, and NK cells. Non-hematopoietic cells: thymic epithelial cells (mTECs), intestinal epithelial cells (enterocytes, microfold cells), lymphatic and endothelial cells (LEC) | (12, 14, 16, 17) |
| BAFF or BLys (TNFSF13B) | SLOs and bone marrow | Leukocytes: monocytes, macrophages, dendritic cells, and neutrophils. Non-hematopoietic cells: LN stromal cells (FRCs, including TRCsa and MRCsa) | BAFFR (TNFRSF13C) | SLOs and bone marrow | Leukocytes: mature B cells (transitional, naïve, GC, and memory B cells) | (12, 14, 18, 19) |
| TWEAK (TNFSF12) | Broad, including bone marrow, SLOs, and liver | Leukocytes: T and Ba cells, NK cells, monocytes, macrophages, dendritic cells, and neutrophils Non-hematopoietic cells: epithelial cells and endothelial cells | Fn14 or TWEAK-R (TNFRSF12A) | Broad, including SLOs | Non-hematopoietic cells: epithelial cells | (12, 20) |
| Ligand (gene) . | Tissue expression . | Cellular expression . | Receptor (gene) . | Tissue expression . | Cellular expression . | Reference . |
|---|---|---|---|---|---|---|
| CD40L or CD154 (CD40LG) | SLOs and thymus | Leukocytes: activated T cells (CD4+, CD8+, and γδ), NKT, MAIT, Tregs, also detected on NK cells, mast cells, basophils, and eosinophils | CD40 or TNFRSF5 (CD40) | SLOs and thymus | Leukocytes: B cells, dendritic cells, monocytes, and macrophages. Non-hematopoietic cells: epithelial cells (mTECs), follicular dendritic cells, endothelial cells, and fibroblasts | (11, 12) |
| LTα1β2 (LTA and LTB) | SLOs, thymus, and bone marrow | Leukocytes: activated B and T cells, NKT, MAIT, Tregs, and dendritic cells | LTβR or TNFRSF3 (LTBR) | SLOs, thymus, and bone marrow | Leukocytes: dendritic cells, monocytes, and macrophages. Non-hematopoietic cells: LN stromal cells (FRCs, including MRCsa), epithelial cells, endothelial cells, and mesenchymal cells | (12, 13, 14) |
| LIGHT (TNFSF14) | Broad, including bone marrow, SLOs, and liver | Leukocytes: T cells, NK cells, macrophages, monocytes, and dendritic cells | ||||
| LIGHT-R or HVEM (TNFRSF14) | Broad, including SLOs | B and T lymphocytes, NK cells, monocytes, macrophages, and dendritic cells | (12, 15) | |||
| RANKL (TNFSF11) | SLOs, bone marrow, bones, and thymus | Leukocytes: activated T and B cells and NK cells. Non-hematopoietic cells: osteoblasts, osteocytes, LN stromal cells (MRCsa), epithelial, and germ cells | RANK (TNFRSF11A) | Gastrointestinal tract, SLOs, and bones | Hematopoietic cells: osteoclasts, macrophages, dendritic cells, and NK cells. Non-hematopoietic cells: thymic epithelial cells (mTECs), intestinal epithelial cells (enterocytes, microfold cells), lymphatic and endothelial cells (LEC) | (12, 14, 16, 17) |
| BAFF or BLys (TNFSF13B) | SLOs and bone marrow | Leukocytes: monocytes, macrophages, dendritic cells, and neutrophils. Non-hematopoietic cells: LN stromal cells (FRCs, including TRCsa and MRCsa) | BAFFR (TNFRSF13C) | SLOs and bone marrow | Leukocytes: mature B cells (transitional, naïve, GC, and memory B cells) | (12, 14, 18, 19) |
| TWEAK (TNFSF12) | Broad, including bone marrow, SLOs, and liver | Leukocytes: T and Ba cells, NK cells, monocytes, macrophages, dendritic cells, and neutrophils Non-hematopoietic cells: epithelial cells and endothelial cells | Fn14 or TWEAK-R (TNFRSF12A) | Broad, including SLOs | Non-hematopoietic cells: epithelial cells | (12, 20) |
Bold typeface is used to indicate the principal cell type in which expression occurs. FRC, fibroblastic reticular cells; LEC, lymphatic endothelial cells; LN, lymph node; MRC, marginal reticular cells; TRC, T-zone reticular cells.
Evidence only at the mRNA level.