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.
Ehirchiou
Driss
D
Center for Vascular and Inflammatory Diseases, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Xiong
Ying
Y
Xu
Guangwu
G
Chen
Wanjun
W
Shi
Yufang
Y
Zhang
Li
L
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D006968:Hypersensitivity, Delayed; D007108:Immune Tolerance; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D039481:CD11b Antigen; D016207:Cytokines; D020381:Interleukin-17