Table 2.
Possible crosstalk pathways between immune cells involved in CSU.
| Cytokine | Receptors | The serum level | Cell sources | Cell targets | Major functions | References |
|---|---|---|---|---|---|---|
| IL-1β | IL-1 type 2 receptor | Increased | Mast cells | Neutrophils | Induction of neutrophils migration and vascular leakage | (97, 177) |
| IL-2 | IL-2R | Decreased | CD4+and CD8+ activated T cells |
CD4+ and CD8+ T cells, B cells |
Proliferation of effector T and B cells; development of Treg cells; growth factor for B cells and stimulus for antibody synthesis | (75, 76, 189) |
| IL-3 | IL-3 receptor α+β c (CD131) |
Increased (in lesions) | T cells, macrophages, Mast cells, NK cells, eosinophils |
Basophils, eosinophils | Activation of basophils and eosinophils; up-regulate the expression of FcϵRI in basophils and improvement of cell viability |
(62, 113, 115, 116) |
| IL-4 | IL-4R type I, IL-4R type II |
Increased | Th2 cells, Basophils, Mast cells |
T cells, B cells, Mast cells, monocytes | Activation of basophils and T cells; enhancement of humoral immunity; recruitment of eosinophils; Induction of monocytes and Th2 differentiation; survival factor for B and T cells | (70, 117, 119, 124, 125, 178, 204) |
| IL-5 | IL-5R | Increased | Mast cells, Th2 cells, activated eosinophils |
Eosinophils, basophils | Increment of eosinophils chemotactic activity and adhesion capacity |
(96, 147, 205) |
| IL-6 | IL-6R (sIL-6R) gp130 |
Increased | T cells, basophils, mast cells, macrophages | B cells, mast cells | B-cell differentiation and production of IgG, IgM, and IgA; Enhancement of mast cell proliferation, maturation, and reactivity |
(62, 89, 177, 206, 207) |
| IL-8 | CXCR1 and CXCR2 |
Increased | Mast cells, eosinophils | Neutrophils, NK cells, T cells, basophils, and eosinophils |
Chemoattractant for neutrophils, NK cells, T cells, basophils, and eosinophils |
(95, 170, 172, 208, 209) |
| IL-9 | IL-9R | Increased | T cells, mast cells, eosinophils |
B, T, and mast cells | T cell and mast cell growth factor; inhibition of Th1-cytokines; proliferation of CD8+ T cells and mast cells |
(70, 80–82, 210) |
| IL-10 | IL-10R1/IL-10R2 complex |
Increased | T cells, B cells | T cells, B cells | Inhibition of the function of Th1 and Tc1; activation of B cells and induction of autoantibodies by B cells | (80, 83, 211, 212) |
| IL-13 | IL-13R1a1 and IL-13R1a2 |
Increased | T, NKT, and mast cells, basophils and eosinophils |
B cells, mast cells, eosinophils | Activation of eosinophils and mast cells; recruitment and survival of eosinophils |
(78, 213, 214) |
| IL-17 | IL-17R | Increased | Th17 cells | Monocytes, macrophages, B and T cells |
Induction of proinflammatory cytokines, chemokines, and metalloproteases; recruitment and activation of neutrophils |
(77, 215–217) |
| IL-18 | IL-18R | Increased | Macrophages | T cells, NK cells, macrophages |
Induction of IFN-γ in the presence of IL-12; enhancement of NK cell cytotoxicity, promoting Th1 or Th2 cell responses depending on cytokine milieu |
(92–94, 218, 219) |
| IL-21 | IL-21R | Decreased | T cells | CD4+T cells, CD8+T cells, B cells, DCs, macrophages |
Induction of antigen-specific B-cell apoptosis; inhibition of B-cell proliferation | (119, 186, 202) |
| IL-23 | IL-23R | Increased | Macrophages | T cells (Th17 cells), NK cells, eosinophils, monocytes, macrophages |
A supporting role in the continued stimulation and survival of Th17 cells; induction of the secretion of IL-17 by non-T cells | (77, 219) |
| IL-24 | L-20R1/IL-20R2 and IL-22R1/ IL-20R2 |
Increased (in lesions) | T cells, monocytes, B cells |
Mast cells | An autoantigen in chronic spontaneous urticaria; | (16, 220) |
| IL-25 | IL-17RA and IL-17RB |
Increased (in lesions) | T cells, mast cells, eosinophils, basophils | Th2 memory cells, basophils, NKT cells, macrophages |
Induction of Th2 responses and inhibition of both Th1 and Th17 responses; induction of IgE, IgG1, IL-4, IL-5, IL-9, IL-13 production | (71) |
| IL-31 | IL-31RA/OSMRβ | Increased | T cells, mast cells, basophils | Eosinophils, mast cells, basophils | Induction of IL-6, IL-8, CXCL1, CXCL8, CCL2, and CCL8 production in eosinophils |
(129, 130, 134, 221) |
| IL-33 | ST2 | Increased | Th2 cells, macrophages, mast cells, eosinophils, basophils | Basophils, mast cells, eosinophils, DCs, macrophages, NK cells, NKT cells, T lymphocytes, B lymphocytes |
Enhanced integrin expression in basophils and eosinophils; induction of the synthesis and secretion of IL-31 by mast cells; enhancement of allergic stimulation of mast cells and basophils; promotion of mast cells maturation |
(93, 129, 131, 133, 134) |
| IL-35 | IL-12Rβ2/gp130; IL-12Rβ2/IL-12Rβ2; gp130/gp130 |
Decreased | Treg cells, monocytes | NK cells and activated T cells |
Reduction of effector T-cell proliferation; Increase of IL-10 production and Treg proliferation | (222–224) |
| TNFα | TNFR1 (p55/60, CD120a) and TNFR2 (p75/80, CD120b) |
Increased | T cells, mast cells, basophils | Eosinophils | Activation of eosinophils; Increase the expression of eosinophils ICAM-1 | (75–77, 225, 226) |
| IFN-γ | IFNGR1/IFNGR2 | Decreased | T cells, mast cells, macrophages | Eosinophils, lymphocytes, mast cells, macrophages, and neutrophils | Aggregation of eosinophils, lymphocytes, mast cells, macrophages, and neutrophils | (71, 75, 76, 117, 206, 227) |
| IFN-λ1 | IFNLR1 and IL-10R2 |
Increased (in plasma) | T cells, macrophages, mast cells | Eosinophils, lymphocytes, mast cells, macrophages, and neutrophils | regulation of Th1/Th2 responses | (91, 182) |
| TGF-β | TβR-I and TβR-II | Increased | Eosinophils, macrophages, Treg cells |
T cells, NK cells, monocytes, macrophages, neutrophils, and eosinophils |
Reduction of mast cells expression of FcϵRI; regulation of the differentiation of several Th cell subsets and induction of Treg cells; immune tolerance |
(146) |