Table 1 Immune-regulatory mediators secreted by epithelial cells
From: Role of microRNAs in immunoregulatory functions of epithelial cells
Factors | Epithelial cell type | Function | References |
|---|---|---|---|
IL-8 | Cornea, Intestine, Caco2 cells, T84 cells, HeLa cells, Bronchus, A549 cells, HaCaT cells, NHEKs, Mouse skin, Goat mammary, Colon, IB3-1 cells, Human skin and gingival keratinocytes | - Chemoattraction and activation of polymorphonuclear leukocytes, including neutrophils and basophils -Angiogenesis | |
IL-6 | Caco-2 cells, A549 cells, HaCaT cells, NHEKs, Mouse skin, IB3-1 cells, Human and rat corneas | - Involved in both pro-inflammatory and anti-inflammatory responses [68] | |
IL-1β | Caco-2 cells, Skin of psoriatic patients, Human keratinocyte, HaCaT cells, NHEKs, Mouse skin, Goat mammary, Human cornea | - Inflammatory cytokine - Induction of insulin resistance in human keratinocytes via p38MAPK (mitogen-activated protein kinase), which blocks insulin-dependent differentiation of these cells - Proliferation of keratinocytes | |
TNF-α | Caco-2 cells, A549 cells, Mouse skin, Human keratinocyte, Human and rat cornea | - Inflammatory cytokine | |
IL-1α | A549 cells | - Inflammatory cytokine | [65] |
IFN-β | A549 cells | - Inflammatory cytokine | |
IL-12 | A549 cells | - Inflammatory cytokine | |
IL-10 | A549 cells, Human cornea | - Anti-inflammatory cytokine | |
IL-13 | A549 cells | - Anti-inflammatory cytokine | [20] |
IL-17 | A549 cells | -A pro-inflammatory cytokine which may contribute to the recruitment of the immune cells such as neutrophils | [20] |
M-CSF | HT29 cells, Intestine | - A pro-inflammatory cytokine - Serves as a chemoattractant which recruits macrophages to the infection site and activates them to phagocytose and kill foreign microorganisms | [74] |
G-CSF | A549 cells | - Acts as an anti-inflammatory cytokine [75] - Exerts pivotal regulatory effects in hematopoiesis and immune responses [76] - Prevents overactivation of monocytes and lymphocytes by reducing the release of pro-inflammatory mediators and concomitantly activating the anti-inflammatory defense of neutrophils [75] - Stimulates granulocyte production, maturation, and migration to the infection site [20, 76] - Promotes T cell tolerance in pathological conditions associated with a Th1/Th2 imbalance [76] | [20] |
GM-CSF | A549 cells | - A hematopoietic growth factor that induces the generation of granulocyte and macrophage populations from precursor cells [77, 78] - Promotes the survival, activation, and migration of macrophages, neutrophils, and eosinophils, as well as DC differentiation and maturation [20, 77] - Acts as an immune-modulatory cytokine which has a pivotal role in regulating the immune response and maintaining immunological tolerance [78] | [20] |
IFN-γ | A549 cells | - Pro-inflammatory cytokine | [20] |
TSLP | Intestine, Caco2 cells,, Skin | - An IL-7-like cytokine that acts as a key mediator of epithelial cell–T cell crosstalk - In co-operation with other mediators such as TGF-β, induces the DCs and macrophages with tolerogenic properties - Promotes Th2 cell differentiation and activation while repressing the Th1 arm - Induces ILC2 in the skin | |
RELMβ | Intestine | - A goblet cell-specific effector whose expression is mainly induced by the Th2 antiparasitic cytokine (IL-13)-dependent response in the intestine | [79] |
CCL20 (MIP-3α) | Human keratinocyte, Colon | - A chemotactic cytokine that induces the migration of cells such as DC and lymphocytes and plays an important role at skin and mucosal surfaces under homeostatic or inflammatory conditions [81] | |
IL-25 (IL-17E) | Tuft cells, Bronchus, Nose, Lung, Keratinocyte | - An alarming molecule which can be released extracellularly by cellular damage - Enhances Th2 cell differentiation and Th2 cell-mediated immune responses by inducing the expression of its cytokines, such as IL-4, IL-5, and IL-13 - Stimulates ILC2 to produce cytokines (such as IL-4 and IL-13) in response to helminth and skin challenge - Promotes eosinophilic inflammation and plays roles in the development of allergen-induced disorders - Induces keratinocyte proliferation and production of inflammatory cytokines [82] | |
IL-33a | Keratinocytes, Bronchus, Skin | - A potent stimulus for the activation and migration of skin-derived ILC2s - Induces a Th2- type immune response | |
TGF-β | Intestine, Caco2 cells | - In co-operation with other mediators such as TSLP, implicates in the differentiation of tolerogenic DC and macrophage in response to commensal bacteria-derived stimuli | [55] |
IL-7 | Intestine, A549 cells | - A major survival factor for mature T cells - Promotes the development and homeostasis of T cells, B cells, ILCs, and macrophages - Induces proliferation of naive and memory T cells and enhances effector T cell responses, preferentially Th1 and Th17 responses - Regulates the homeostasis of intestinal ECs, colon function, and the composition of the commensal microflora - Contributes to early immune activation in response to enteric bacterial infection | |
APRIL (TNFSF13) | Intestine, Primary keratinocytes, HaCaT cells, normal renal tissue, renal cell carcinomas, HepG2 and Hep3B cells, hepatocellular carcinoma (HCC) tissue, normal liver | - Is involved in B lymphocyte development, proliferation, and differentiation [88, 89] - Is required for immunoglobulin class switch recombination in B cells [90] - Promotes the development and progression of various cancer cell lines and tumors [89, 91]; but suppression the proliferation of HCC cell lines (HepG2 and Hep3B) by that was also reported [88] | |
BAFF (TNFSF13B) | Intestine, Primary keratinocytes, HaCaT cells, normal renal tissue, renal cell carcinomas, HepG2 and Hep3B cells, HCC tissue, normal liver | - Induces immunoglobulin (IgA1 and, to some extent, IgA2) class switch recombination in B cells [90] - Involved in B lymphocyte proliferation, differentiation [88], and survival [91] | |
MIP-2α (CXCL2) | Human colon | - Chemotactic cytokine | [67] |
MIP-1α | A549 cells | - Chemotactic chemokine | [20] |
MCP-1 (CCL2) | HaCaT cells, NHEKs, Mouse skin, Human colon; A549 cells | - Pro-inflammatory cytokine - Recruits monocytes, T cells, and dendritic cells [82] - Regulates cell proliferation and cell-cycle progression [82] | |
CCL4 | Goat mammary | - Inflammatory response - Chemotaxis | [66] |
CXCL1 (GRO1) | HaCaT cells, Human colon, Human and rat cornea, Human skin and gingival keratinocytes | - A member of the CXC chemokine subfamily - Involved in chemoattraction of neutrophils [93] |