. 2014 Aug 7;20(29):9653–9664. doi: 10.3748/wjg.v20.i29.9653

Table 1.

Summary of information available regarding classification of gut antigen-presenting cells, primary functions of gut antigen-presenting cells and their effects on T-cells, tolerogenic and inflammatory properties of antigen-presenting cells at intestinal sites, and effects of immunomodulation of gut antigen-presenting cells by the microbiota

Classification	Dendritic cells	Macrophages	B-cells
	Mice: CD11c^hi MHC Class II⁺ CX3CR1^-/med F4/80^- CD64^-. Subsets based on CD11b, CD103 and CD8á expression Humans: HLA-DR⁺ Lineage cocktail (CD3/CD14/CD16/CD19/CD34)^-. Subsets based on CD103, CD11c, CD1c, CD141 and CD123 expression	Mice: CD11c⁺ MHC Class II⁺ F4/80⁺ CD68⁺ CD64⁺ CX3CR1^hi Subsets based on levels of expression of CX3CR1. Ly6C⁺ in inflammation Humans: HLA-DR⁺ CD11c⁺ CD64⁺ CD68⁺ Some CX3CR1 expression	CD19⁺ CD20⁺ CD79a⁺ Immature B-cells: ⁺CD20 Plasma (antibody secreting) cells: CD38⁺CD138⁺
Primary function	Antigen sampling Migration to secondary lymphoid tissue and stimulation of naïve T-cells to generate primary T-cell responses	Antigen sampling Phagocytosis of apoptotic cells, bactericidal activity, production of anti-inflammatory IL-10	Antibody secretion as differentiated plasma cells (mainly IgA in the gut)
Effects on T-cells	Determine whether primary T-cell responses are immunogenic or tolerogenic, imprint gut-homing receptors on T-cells during stimulation	Contribute to effector T-cell responses in situ in the lamina propria, including expansion and differentiation of T-regs via IL-10 production	Contribute to effector T-cell responses in situ in lamina propria and also induce differentiation of T-regs via both IL-10 production and direct interaction
Tolerogenic properties/subsets	CD103⁺ CD11b^- DC generate RA for T-regs/IgA secretion by B-cells, and imprinting gut-homing properties on lymphocytes. CD8á⁺ DC and pDC generate T-reg Gut DC in general are hyporesponsive to TLR stimulation	CX3CR1^hi MФ produce IL-10 critical for T-reg generation Hyporesponsive to TLR stimulation	IgA production limits immune responses against commensal bacteria Regulatory B-cells produce IL-10, induce differentiation of T-regs and also produce TGFβ
Inflammatory properties/subsets	TLR^hi gut DC in IBD likely to contribute to enhanced inappropriate responses to the microbiota Infiltrates of CD103^- DC in inflammation CD103⁺CD11b⁺ can polarise inflammatory Th17 responses	TLR^hi MФ in colitis and IBD also likely to contribute to enhanced inappropriate responses to the microbiota Ly6C⁺CX3CR1⁺ inflammatory macrophages arise from arrested differentiation in colitis	TLR^hi B-cells enhanced in IBD Eotaxin-1 producing B-cells enhanced in IBD CD15⁺ B-cells with functional surface IgM enhanced in IBD
Modulation by gut microbiota	Direct modulation by microbiota Commensal bacteria can induce iNOS⁺TNF⁺ DC that promote IgA responses Commensal bacteria induce regulatory cytokine production by DC, such as IL-10 and TGFβ, and also regulatory mediator RA	Direct modulation by microbiota CX3CR1⁺ MФ directly sample luminal antigens; this process is dependent on the microbiota	Indirect modulation by microbiota DC and MФ sampling commensal bacteria induce IgA production by B-cells via BAFF and APRIL release, and production of IgA-inducing cytokines IL-10 and TGFβ

TGFβ: Transforming growth factor beta; TNF: Tumor necrosis factor; DC: Dendritic cells; MΦ: Macrophages; IL-10: Interleukin 10; T-reg: Regulatory T cells; TLR: Toll-like receptors; pDC: Plasmacytoid DC; RA: Retinoic acid; HLA: Human leukocyte antigen; IBD: Inflammatory bowel disease.