Immune Netw.  2016 Feb;16(1):1-12. 10.4110/in.2016.16.1.1.

Regulation of Th2 Cell Immunity by Dendritic Cells

• Na H
• Cho M
• Chung Y

• KMID: 2154806
• DOI: http://doi.org/10.4110/in.2016.16.1.1

Abstract

Th2 cell immunity is required for host defense against helminths, but it is detrimental in allergic diseases in humans. Unlike Th1 cell and Th17 cell subsets, the mechanism by which dendritic cells modulate Th2 cell responses has been obscure, in part because of the inability of dendritic cells to provide IL-4, which is indispensable for Th2 cell lineage commitment. In this regard, immune cells other than dendritic cells, such as basophils and innate lymphoid cells, have been suggested as Th2 cell inducers. More recently, multiple independent researchers have shown that specialized subsets of dendritic cells mediate Th2 cell responses. This review will discuss the current understanding related to the regulation of Th2 cell responses by dendritic cells and other immune cells.

Keyword

Th2 cell; Dendritic cell; PDL2; CD301b; Allergic inflammation

MeSH Terms

Basophils
Dendritic Cells*
Helminths
Humans
Interleukin-4
Lymphocytes
Th1 Cells
Th17 Cells
Th2 Cells*
Interleukin-4

Figure

• 

  Figure 1 Modulation of DC functions by Th2 cell-skewing stimuli. The stimulation of epithelial cells by allergens and infectious agents results in the production of TSLP, IL-25, and IL-33, leading to the upregulation of the Notch ligand Jagged 1, OX40L, and chemokine release. These chemokines attract basophils that release IL-4 and cooperate with DCs to induce Th2 responses. Glycans from HDM are recognized by Dectin-2 and induce Th2 responses by producing cysteinyl leukotrienes. The enzyme omega-1 from S. mansoni is internalized by mannose receptors of DCs and degrades rRNA and mRNA, leading to the inhibition of protein synthesis. Pam-3-Cys signals through TLR2 and activates ERK. c-Fos phosphorylation by ERK inhibits the production of IL-12p70, which is a key inducer of Th2 differentiation. LPS from P. gingivalis induces Th2 responses through TLR4 signaling. Alum or damage causes necrosis and release of HMGN1 and uric acid crystals, which function as a danger signal. HMGN1 polarize DCs to induce Th2 responses in a TLR4-dependent manner. Abbreviations: HDM, house dust mite; HMGN1, high-mobility group nucleosome-binding protein 1; MR, mannose receptor; TLR, toll-like receptor; TSLP, thymic stromal lymphopoietin; Th, T helper cell.

• 

  Figure 2 Proposed phenotypes of type 2 DCs. Conventional DCs commonly express CD11c and MHC class II. Type 2 DCs exhibit the specialized surface markers CD301b, PDL2, and CD11b and several receptors for Th2 cell-related cytokines such as IL-4R, IL-13R, IL-25R, TSLPR, and T1/ST2 (IL-33R). Signaling through cytokine receptors upregulates the expression of PDL2 and CD301b. Additionally, the ERK and STAT5 pathway upregulates CD40, OX40L, and Jagged. Activation of the major transcription factors IRF4 and KLF4 inhibits IL-12 production and increases IL-10 secretion. FcεRIII displayed by type 2 DCs is responsible for inducing IgG1-related Th2 responses. Altogether, these factors trigger Th2 polarization.

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