Death receptor 3 signaling enhances proliferation of human regulatory T cells.
Exploiting regulatory T cells (Tregs) to control aberrant immune reactions is a promising therapeutic approach, but is hampered by their relative paucity. In mice, activation of death receptor 3 (DR3), a member of the TNF-receptor superfamily (TNFRSF), increases Treg frequency and efficiently controls exuberant immune activation. For human Tregs, neither DR3 expression nor potential functions have been described. Here, we show that human Tregs express DR3 and demonstrate DR3-mediated activation of p38, ERK, and NFκB. DR3 stimulation enhances Treg expansion ex vivo while retaining their suppressive capacity. In summary, our results establish a functional role for DR3 signaling in human Tregs and could potentially help to tailor Treg-based therapies.
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Germany.
Sebastian
S
Bittner
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Germany.
Gertrud
G
Knoll
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Germany.
Martin
0000-0003-4681-8628
M
Ehrenschwender
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000187:drug effects; D052003:NF-kappa B p52 Subunit / Q000819:agonists* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D007166:Immunosuppressive Agents; D008024:Ligands; D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human; D010446:Peptide Fragments; D020033:Protein Isoforms; D053219:Receptors, Tumor Necrosis Factor, Member 25; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; C415902:TNFRSF1B protein, human; C506033:TNFRSF25 protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D020123:Sirolimus
DR3; TL1A; TNFRSF25; TNFSF15; Treg