Abstract
Inappropriate activation of T helper (Th) cells, such as Th1 and Th17 cells, is implicated in the pathogenesis of chronic inflammatory disorders including ulcerative colitis (UC). CX3CR1high macrophages contribute to intestinal homeostasis through various mechanisms in mice. However, whether mononuclear phagocytes with regulatory functions are present in the human colon is not clearly defined. We investigated whether innate myeloid cells that suppress activation of effector T cells exist in the human intestinal mucosa. Among intestinal lamina propria cells, Lin- HLA-DRhigh CD14+ CD163high cells were subdivided into CD160low and CD160high cells. Both subsets produced high levels of IL-10. CD163high CD160high cells suppressed effector T cell proliferation, whereas CD163high CD160low cells induced Th17 differentiation. Patients with UC exhibited increased numbers of CD163high CD160low cells, while showing profoundly decreased numbers of CD163high CD160high cells. In this context, CD163high CD160high cells had higher CD80/CD86 expression and lower IL10RB expression, and these cells did not suppress effector T cell proliferation. The CD163high CD160high subset in normal intestinal mucosa inhibits inappropriate Th1/Th17 responses through suppression of their proliferation, and its number and suppressive activity are impaired in patients with UC. These findings indicate how human innate immune cells might prevent UC development.