SHIP-deficient, alternatively activated macrophages protect mice during DSS-induced colitis

m phi are heterogeneous in their functions, and although it is clear that inflammatory m phi contribute to inflammation in IBDs, multiple lines of evidence suggest that M2a m phi may offer protection during intestinal inflammation. In vivo SHIP-deficient mouse m phi are M2a so SHIP-deficient mice provide a unique genetic model of M2a m phi. Based on this, this study tested the hypothesis that SHIP-deficient, M2a m phi protect mice from intestinal inflammation. The objectives were to compare the susceptibility of SHIP+/+ and SHIP-/- littermates with DSS-induced intestinal inflammation and to determine whether protection was m phi-mediated and whether protection could be transferred to a susceptible host. We have found that SHIP-/- mice are protected during DSS-induced intestinal inflammation. SHIP-/- mice have delayed rectal bleeding and reduced weight loss, disruption of intestinal architecture, and immune cell infiltration during DSS-induced colitis relative to their WT littermates. Using liposome depletion of m phi, we found that SHIP-/- mouse protection was indeed m phi-mediated. Finally, we determined that SHIP-/- m phi-mediated protection could be conferred to susceptible WT mice by adoptive transfer of M2a m phi derived ex vivo. This study supports our hypothesis by demonstrating that SHIP-deficient, M2a m phi are protective in this murine model of acute intestinal inflammation. Adoptive transfer of M2a m phi to patients with IBDs offers a promising, new strategy for treatment that may be particularly useful in patients who are otherwise refractory to conventional therapies. J. Leukoc. Biol. 90: 483-492; 2011.