786 The Pharmacokinetics of Infliximab Induction Therapy in Patients With Moderate to Severe Ulcerative Colitis

G A A b st ra ct s of anti-inflammatory M2 BMDM, determined by expression of Arg1 and Fizz1 that are classical M2 markers, was impaired in Il10rb-/mice. These Mφ also expressed significantly higher levels of pro-inflammatory cytokines following LPS stimulation, suggesting that IL10R signaling regulates TLR4-dependent responses in murine anti-inflammatory Mφ. Il10rb-/M2 Mφ also produced less IL10 and promoted less generation of Tregs in-vitro, perhaps due to decreased surface expression of PD-L1 and PD-L2. Moreover, transfer of WT but not Il10rb-/M2 Mφ ameliorated CD4+-induced colitis in Il10rb-/-Rag2-/mice. Similar to murine studies, the generation of M2 Mφ was severely impaired in human IL10R deficient patients. These Mφ also secreted significantly higher levels of TNF, IL6 and IL12 following LPS stimulation, and promoted less generation of Tregs. Conclusion: IL10R-dependent signals play a critical role in the generation and function of blood borne and tissue resident anti-inflammatory Mφ in mice and humans. Therapeutics and cell-based therapies aimed at augmenting anti-inflammatory Mφ may have clinical utility.