Identification of a human intestinal myeloid cell subset that regulates gut homeostasis

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). CX(3)CR1(high) 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(+) CD163(high) cells were subdivided into CD160(low) and CD160(high) cells. Both subsets produced high levels of IL-10. CD163(high) CD160(high) cells suppressed effector T cell proliferation, whereas CD163(high) CD160(low) cells induced Th17 differentiation. Patients with UC exhibited increased numbers of CD163(high) CD160(low) cells, while showing profoundly decreased numbers of CD163(high) CD160(high) cells. In this context, CD163(high) CD160(high) cells had higher CD80/CD86 expression and lower IL10RB expression, and these cells did not suppress effector T cell proliferation. The CD163(high) CD160(high) 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.