TLR4 and necrotizing enterocolitis: ,6 Studies on human intestinal tissues derived from preterm infants with NEC also have suggested that genes that mediate TLR signaling such as TLR4, myeloid differentiation primary response 88 (MYD88), and downstream cytokines are increased in NEC, while negative regulators of TLR signaling such as single immunoglobulin interleukin-1–related receptor (SIGIRR) and A20 have decreased expression in NEC.7