ICOS and Sepsis: However, the effectiveness of ICOS-Fc not only in WT mice but also in ICOS-/- mice, lacking the endogenous ICOS, strongly suggest that the main protective effect on sepsis is due to triggering of ICOSL, which is in line with previous works showing that ICOSL triggering by ICOS-Fc elicits several anti-inflammatory activities both in vitro and in vivo (13, 15, 16, 19).