Th22 cells (T helper cells type 22) are subpopulation of

CD4+ T cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...

that produce interleukin-22 ( IL-22). They play a role in the protective mechanisms against variety of bacterial pathogens, tissue repair and wound healing, and also in pathologic processes, including inflammations,

autoimmunity In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease ...

, tumors, and digestive organs damages.

Characterization

Th22 cells are mainly defined by their high secretion of interleukin-22 ( IL-22). Besides IL-22, Th22 cells also produce other cytokines, such as interleukin-13 ( IL-13) and tumor necrosis factor alpha (

TNF-alpha Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

), but in very small quantities. Additionally, they could be characterized by their cell surface expression of CD3,

CD4 In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic c ...

CD28 CD28 (Cluster of Differentiation 28) is a protein expressed on T cells that provides essential co-stimulation, co-stimulatory signals required for T cell activation and survival. When T cells are stimulated through CD28 in conjunction with the T- ...

, number of

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

receptors

CCR10 C-C chemokine receptor type 10 is a protein that in humans is encoded by the ''CCR10'' gene. Function Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of v ...

CCR6 Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the ''CCR6'' gene. CCR6 has also recently been designated CD196 (cluster of differentiation 196). The gene is located on the long arm of C ...

CCR4 C-C chemokine receptor type 4 is a protein that in humans is encoded by the ''CCR4'' gene. CCR4 has also been designated CD194 ( cluster of differentiation 194). The protein encoded by this gene belongs to the G protein-coupled receptor family. ...

that are associated with cutaneous T cell homing, and platelet-derived growth factor receptor ( PGDFR).

Differentiation

Th22 cells differentiate from naive T-lymphocytes in presence of number of

cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

and

transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...

Cytokines in differentiation

Activated naive

differentiate into Th22 cells under the influence of interleukin-6 ( IL-6) and tumor necrosis factor alpha (

). This process can be inhibited by the addition of increasing concentrations of transforming growth factor beta (

TGF-beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other ...

). The combination of interleukin-21 ( IL-21) and interleukin-23 ( IL-23) can also induce the differentiation of

naive T cells In immunology, a naive T cell (Th0 cell) is a T cell that has differentiated in the thymus, and successfully undergone the positive and negative processes of central selection in the thymus. Among these are the naive forms of helper T cells (CD4 ...

into Th22 cells via the endogenous toll-like receptor 4 ligand (

TLR4 Toll-like receptor 4 (TLR4), also designated as CD284 (cluster of differentiation 284), is a key activator of the innate immune response and plays a central role in the fight against bacterial infections. TLR4 is a transmembrane protein of approx ...

), stimulating

keratinocytes Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes refer ...

to secrete interleukin-23 ( IL-23) and binds to the IL-23 receptor of skin

dendritic cells A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

. This mechanism induces the differentiation into Th22 cells and secretion of interleukin-22 ( IL−22).

Transcription factors in differentiation

Downstream signaling of the transcription factor aryl hydrocarbon receptor (

AHR Ahr () is a river in Germany, a left tributary of the Rhine. Its source is at an elevation of approximately above sea level in Blankenheim in the Eifel, in the cellar of a timber-frame house near the castle of Blankenheim. After it crosses f ...

) is essential for Th22 production of interleukin-22 ( IL-22). RORγt acts as a positive transcription factor and

T-bet T-box transcription factor TBX21, also called T-bet (T-box expressed in T cells), is a protein that in humans is encoded by the ''TBX21'' gene. Though being for long thought of only as a master regulator of type 1 immune response, T-bet has recen ...

acts as a negative transcription factor for Th22 cell differentiation. However, additional intracellular molecules involved in Th22 differentiation are still being investigated.

Physiological functions

Through their production of interleukin-22 ( IL-22), Th22 cells have been shown to be protective against a number of bacterial and viral pathogens. Interleukin-22 ( IL-22) regulates different innate immune mechanisms to eliminate infiltration of invasive pathogens into the skin, gut and respiratory tract. Interleukin-22 ( IL-22) influences

and epithelial cells to stimulate proliferation and differentiation, thus promoting wound healing and cohesion of barrier integrity. Interleukin-22 ( IL-22) also enhances stromal secretion of

antimicrobial peptides Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between Prokaryote, prokaryotic and eukaryota, eukaryotic cells that may ...

, as well as production of the

chemokines Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

which promote recruitment of other immune cells.

Th22 in diseases

Th22 has both pathologic and protective claimed roles when maintaining immunologic homeostasis. However, the role of Th22 in pathological processes has not been completely identified.

AIDS

It seems that Th22 cells could play a protective role in patients with

AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

CCR5 C-C chemokine receptor type 5, also known as CCR5 or CD195, is a protein on the surface of white blood cells that is involved in the immune system as it acts as a receptor for chemokines. In humans, the ''CCR5'' gene that encodes the CCR5 p ...

and α4β7 molecules expressed by Th22 cells were able to bind to the circulating HIV receptor, and thus via interleukin-22 ( IL-22) production protect against intestinal epithelial damage, leading to a mechanism of resistance against HIV-induced destruction of epithelial cell integrity.

Psoriasis

In psoriasis Th22 cells have been causally linked to pathological processes. In patients with psoriasis the levels of Th22 cells and interleukin-22 ( IL-22) were increased. High levels of interleukin-22 ( IL-22) together with interleukin-6 ( IL-6) can induce the expression of antimicrobial proteins ( AMPs), and stimulate the

to secrete proinflammatory mediators and

in the skin. In addition, it can also inhibit keratinocyte differentiation and inhibit the normal skin healing process.

Systemic lupus erythematosus

The role of Th22 cells in systematic lupus erythematous (

SLE Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...

) is still unclear. In some patients levels of Th22 cells and interleukin-22 ( IL-22) were increased, which correlated with disease activity, but decreased levels of interleukin-22 ( IL-22) and Th22 cells were also reported. Interleukin-22 ( IL-22) is a cytokine involved in recruiting

neutrophils Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different ...

in response to microbe invading, and in the case of lupus, it seems that interleukin 22 (IL-22) is involved in inflammatory and pathological processes via recruiting of immune cells. On the other hand, Th22 cells might be a better predictor of systematic lupus erythematous (SLE) development than Th17 cells.

Tumors

Th22 cells are involved in tumorigenesis in cases of hepatocellular carcinoma, liposarcoma or colon cancer, and affect tumor tissue in two different pathways. Overexpression of interleukin-22 ( IL-22) or Th22 cells may result in the progression of cancer growth and cause malignant epithelial cell proliferation. However, physiological functions of Th22 cells are tissue repair and wound healing. Some studies have shown a possible anti-tumor effect of these cells, and normal interleukin-22 ( IL-22) secretion leads to tissue repair.

References

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