Other Cell Type-specific Responses Regulated by TNF Superfamily Members

While many TNF superfamily members initiate apoptosis or are involved in the stimulation and homeostasis of immune cells, other TNF family members mediate alternative biological activities. Although TROY has no known ligand, both TROY and XEDAR are involved in hair follicle formation via NF-kappa B activation. RANK, another TNF family member, initiates osteoclast differentiation via NF-kappa B activation and may play a role in breast cancer metastasis. The Lymphotoxin beta receptor (LT beta R) binds LIGHT as well as heterotrimers composed of Lymphotoxin beta and Lymphotoxin alpha. LT beta R activation is necessary for formation of secondary immune tissues, stimulation of cytokine secretion by mast cells and fibroblasts, and carcinogenesis. TWEAK mediates normal tissue remodeling and is important in disease and cancer.