Working model of the roles of the LT/TNF family members in lymphangiogenesis in inflammation. The putative cellular origin of cytokines of the LT/TNF family is indicated at the top of the figure. In WT mice, all forms of the cytokines are indicated: TNFα₃, LTα₃, and LTα₁β₂. LTα₂β₁ is not included in the figure. The receptors for the various forms of the cytokines are indicated. LTα^−/− mice produce only TNFα₃. Even though these mice make LTβ mRNA, no protein is assembled on the cell surface due to the requirement of LTα for the cell surface expression of LTβ. TNFα₃ and LTα₃ are produced in LTβ^−/− mice. The absence of LTβ allows more LTα to assemble as the LTα₃ homotrimer, and is an explanation for the more intense inflammation in the absence of LTβ. TNFα₃ and LTα₃, working through the TNF receptors induce chemokines and inflammatory vascular adhesion molecules that then induce the accumulation of additional cells that can produce factors, such as VEGFs capable of inducing lymphangiogenesis. It is also possible that LTα₃ and TNFα₃ induce VEGFs directly from stromal cells and could also have direct effects on lymphatic endothelial cells.