Interleukin-22

Interleukins (from Latin/Greek inter = between; leukos = white; kinein = to move) are a group of endogenous, short-chain regulatory proteins (cytokines) of the immune system (IL1-IL38). Interleukins are mediators for induction, course and control of T-cell-mediated cytotoxic immune reactions as well as B-cell activation (antibody production). They are mainly formed and secreted by stimulated leukocytes, monocytes and macrophages. So far, about 38 different interleukins have been clearly identified. Each cytokine of the interleukin group is nomenclatically assigned a number for its classification (IL-1 to IL-38).

Some structurally related substances have been grouped into families. Their members often have a similar function or participate in the fine regulation of immune reactions, for example by regulating the synthesis of related interleukins.

Interleukin-22 (IL-22) is a member of the interleukin-10 cytokine family (Sabat R 2010), which was first described in 2000. The Interleukin-10 family comprises multifunctional cytokines with anti-inflammatory properties that consist in the "regulation" of antigen presentation and macrophage activation. Besides Interleukin-22, the Interleukin-10 family includes: Interleukin -10, Interleukin -19, Interleukin -20, Interleukin-24, Interleukin -26.

IL-22 binds to a heterodimeric cell-surface receptor complex composed of the IL-10R2 and IL-22R1 subunit (Jones 2008). Furthermore, it has been shown that IL-22 also binds to a secreted receptor (IL-22 binding protein, IL-22BP), which is encoded by its own gene. IL22BP is able to inhibit the effect of IL-22 (SAbat R 2011).

The IL-22 receptor is expressed by epithelia and stroma cells, but not by immune cells. In particular, these are: non-hematopoietic cells such as hepatocytes, keratinocytes, epithelia of the bronchial system and intestines. Pancreatic islet cells also express a high density of IL-22 receptors.

Interleukin-22 is expressed by activated NK and T cells (Th22 cell). Type 17 T-helper cells (Th17) and innate lymphoid cells (ILCs) also express IL-22 and initiate a response of innate immunity to invading bacterial pathogens. This response takes place in particular through epithelia of the body surfaces, i.e. through epithelial cells of the respiratory tract, intestine, kidney and skin. IL-22 initiates inflammatory reactions by releasing defensins. Interleukin-22 is able to downregulate barrier proteins of the epiermis (Brüggen M-C et al. 2016) and thus inhibits the terminal differentiation of keratinocytes; this has a pathogenetic significance in atopic dermatitis.

In a dual function, interleukin-22 also exerts a cell-protective effect on the epithelia of the intestine, bronchial system, pancreatic islet cells, kidneys, thymus and skin.

The IL-22/IL-22R1/IL-10R2 complex activates intracellular kinases(JAK1, Tyk2 and MAP kinases) and transcription factors, especially STAT3. The complex induces IL-20 and IL-24 when IL-22R1 is complexed with IL-20R2.

It has been shown that IL-22 is involved in the pathogenesis of psoriasis. For example, IL-22 can inhibit the differentiation of keratinocytes and induced psoriasis-like changes in animal experiments. IL-22 is increasingly expressed in the lesional skin of psoriatic patients. Serum interleukin-22 levels correlate with the severity of poriasis. The preparation Fezakinumab is a fully humanized monoclonal antibody against IL-22, which has already been successfully tested in atopic dermatitis) Interleukin-22.

IL-22 plays an etiopathogenetic role in the development of recurrent hepatitis C after liver transplantation.

In HIV infection, the IL-22 blood level also appears to reflect the pathogenicity of the viral infection.

In scleritis, serum IL-22 levels were significantly elevated and correlated with the activity of the disease.

1. Brüggen M-C et al (2016) Antigen or allergen presentation. In: T. Biedermann et al. (eds.) Allergology. Springer-Verlag Berlin-Heidelberg S 62
2. Dudakov JA et al (2015) Interleukin-22: Immunobiology and Pathology. Annual Review of Immunology 33:747-785
3. Hao JQ (2014) Targeting interleukin-22 in psoriasis. Inflammation 37:94-99.
4. Jones BC et al (2008) Structure of IL-22 bound to its high-affinity IL-22R1 chain. Structure 16:1333-1344.
5. Pestka S et al (2004) Interleukin-10 and related cytokines and receptors. Annual Review of Immunology 22: 929-979.
6. Sabat R (2010) IL-10 family of cytokines. Cytokine Growth Factor Rev 21:315-324.
7. Sabat R et al (2011) Research in practice: IL-22 and IL-20: significance for epithelial homeostasis and psoriasis pathogenesis.
   J Dtsch Dermatol Ges 9:518-523.
8. Weidenbusch M et al (2015) Interleukin-22 in kidney injury and regeneration. On J Physiol Renal Physiol 308:F1041-1046.
9. Wolk K et al.(2004) IL-22 increases the innate immunity of tissues. Immunity 21: 241-254.
10. Xie MH et al (2000) Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R. The Journal of Biological Chemistry 275: 31335-31339.