Snapshot: Cytokines III Cristina M

SnapShot: Cytokines III Cristina M. Tato and Daniel J. Cua Schering-Plough Biopharma (Formerly DNAX Research), Palo Alto, CA 94304, USA

Cytokine Receptor Source Targets Major Function Disease Association TNFα Murine: Macrophages, Neutrophils, Inflammatory; ↓ = disregulated fever; increased TNFR,p55; TNFR,p75 monocytes, T cells, macrophages, promotes activation susceptibility to bacterial infection; others monocytes, and production of enhanced resistance to LPS-induced septic Human: endothelial cells acute-phase proteins shock TNFR,p60; TNFR,p80 ↑ = exacerbation of arthritis and colitis LTα Murine: T cells, B cells Many cell types Promotes activation ↓ = defective response to bacterial TNFR,p55; TNFR,p75 and cytotoxicity; pathogens; absence of peripheral lymph development of lymph nodes and Peyer’s patches Human: nodes and Peyer’s TNFR,p60; TNFR,p80 patches LTβ LTβR T cells, B cells Myeloid cells, other Peripheral lymph ↓ = increased susceptibility to bacterial cell types node development; infection; absence of lymph nodes and proinflammatory Peyer’s patches ↑ = ectopic lymph node formation LIGHTa LTβR, DcR3, HVEM Activated T cells, B cells, NK cells, Costimulatory; ↓ = defective CD8 T cell costimulation monocytes, DCs DCs, other tissue promotes CTL activity TWEAK Fn14 Monocytes, Tissue progenitors, Proinflammatory; macrophages, epithelial, promotes cell growth endothelial endothelial for tissue repair and remodeling APRIL TACI, BAFF-R, BCMA Macrophages, DCs B cell subsets Promotes T cell- ↓ = impaired class switching to IgA independent responses; B cell homeostasis and differentiation BAFF TACI, BAFF-R, BCMA Macrophages, DCs, B cells B cell maturation and ↓ = B cell lymphopenia; defective humoral (BlyS) astrocytes survival immunity ↑ = SLE-like syndrome TL1A DcR3, DR3 Macrophages, Activated T cells Promotes proliferation endothelial cells and cytokine production GITRLa GITR DCs, macrophages, T regulatory cells, Costimulatory B cells, others activated T cells OX40La OX40 Activated T cells, T cells, B cells, Costimulatory; ↓ = impaired humoral responses B cells, DCs, DCs activation and migration monocytes of monocytes CD40La CD40 T cells, monocytes, B cells, APCs Costimulatory; ↓ = defective antibody responses and (CD154) macrophages, others promotes T cell- germinal center formation; hyper-IgM dependent responses; syndrome B cell differentiation ↑ = SLE-like syndrome and class switching FASLa FAS, DcR3 Activated T cells, B APCs, many other Regulatory; ↓ = lymphoproliferative disease and cells, and NK cells cell types proapoptotic systemic autoimmunity CD27La CD27 Activated T cells, B T cells, activated Costimulatory (CD70) cells, DCs, monocytes B cells CD30La CD30 Neutrophils, B cells, T cells, B cells Costimulatory; Viral CD30 blocks Th1 response (CD153) macrophages, promotes proliferation activated T cells and cytokine production 4-1BBLa 41BB Activated T cells, B Activated T cells, Costimulatory; cells, DCs, mono- B cells, DCs promotes activation and cytes, macrophages migration of monocytes TRAILa TRAIL-R1 (DR4), R2 Activated NK cells, Many cell types Costimulatory; ↓ = defective NK-mediated antitumor (DR5), R3 (DcR1), T cells promotes NK cell response and R4 (DcR2) functions; proapoptotic ↑ = enhanced responsiveness to autoantigens RANK RANK receptor or T cells and Osteoclasts, many Costimulatory; ↓ = osteopetrosis Liganda osteoprotegrin osteoblasts cell types promotes osteoclasto- ↑ = osteoporosis (TRANCE) genesis and cytokine production aKnown to exhibit bidirectional signaling via the ligand as well as the receptor.

900 Cell 132, March 7, 2008 ©2008 Elsevier Inc. DOI 10.1016/j.cell.2008.02.023 See online version for abbreviations and references. SnapShot: Cytokines III Cristina M. Tato and Daniel J. Cua Schering-Plough Biopharma (Formerly DNAX Research), Palo Alto, CA 94304, USA

Abbreviations TNFα, tumor necrosis factor alpha; DCs, dendritic cells; LT, lymphotoxin; APC, antigen-presenting cell; LIGHT, homologous to lymphotoxin, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed on T cells; HVEM, herpesvirus entry mediator; DcR, decoy receptor; TWEAK, TNF- related weak inducer of apoptosis; APRIL, a proliferation-inducing ligand; BAFF, B cell-activating factor; BCMA, B cell maturation protein A; TACI, transmembrane activator and CAML interactor; SLE, systemic lupus erythematosus; DR, death receptor; GITRL, glucocorticoid-induced TNF receptor ligand; TRAIL, TNF-like apoptosis-inducing ligand; RANK, receptor activator of NF-κB.

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