The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

Dendritic cells (DC) constitute the most potent antigen presenting cells of the immune system, playing a key role bridging innate and adaptive immune responses. Specialized DC subsets differ depending on their origin, tissue location and the influence of trophic factors, the latter remain to be fully understood. Myeloid-associated lymphotoxin-beta receptor (LTbetaR) signaling is required for the local proliferation of lymphoid tissue DC. This review focuses on the LTbetaR signaling cascade as a crucial positive trophic signal in the homeostasis of DC subsets. The noncanonical coreceptor pathway comprised of the immunoglobulin (Ig) superfamily member, B and T lymphocyte attenuator (BTLA) and TNFR superfamily member, herpesvirus entry mediator (HVEM) counter regulates the trophic signaling by LTbetaR. Together both pathways form an integrated signaling circuit achieving homeostasis of DC subsets.