CD11b facilitates the development of peripheral tolerance by suppressing Th17 differentiation.
Antigen-induced immune suppression, like T cell activation, requires antigen-presenting cells (APCs); however, the role of APCs in mediating these opposing effects is not well understood, especially in vivo. We report that genetic inactivation of CD11b, which is a CD18 subfamily of integrin receptors that is highly expressed on APCs, abolishes orally induced peripheral immune tolerance (oral tolerance) without compromising APC maturation or antigen-specific immune activation. The defective oral tolerance in CD11b(-/-) mice can be restored by adoptive transfer of wild-type APCs. CD11b deficiency leads to enhanced interleukin (IL) 6 production by APCs, which subsequently promotes preferential differentiation of naive T cells to T helper 17 (Th17) cells, which are a T cell lineage characterized by their production of IL-17. Consequently, antigen feeding and immunization of CD11b(-/-) mice results in significant production of IL-17 within the draining lymph nodes that interferes with the establishment of oral tolerance. Together, we conclude that CD11b facilitates oral tolerance by suppressing Th17 immune differentiation.
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