T helper cell 22

T helper cell 22, also known as the Th22 cell, are a type of immune cell. Th22 cells are a subset of naïve CD4+ T cells induced by the ligand activation of the transcription factor aryl hydrocarbon receptor (AhR),[1] which uses environmental, metabolic, microbial, and dietary cues to control complex transcriptional programmes.[2]  Th22 cell function is mediated by its ligand specific cytokine interleukin-22 (IL-22).[3]

Differentiation and cytokine expression

Th22 cells were distinguished as their own class of T helper cells due to their production of IL-22, setting them apart from the key expression cytokines of IFN-gamma, IL-4, or IL-17 that are associated with Th1, Th2, and Th17 cells respectively.[1][4] Th22 cell differentiation is stimulated by IL-6 and TNF-alpha, but others have found Th22 can be stimulated using Langerhans cells and dermal dendritic cells.[3] Th22 cells are known to secrete IL-22, IL-13, IL-26, TNF-α, and granzyme B.[5]

In the immune response

Th22 cells express the chemokine receptors CCR4, CCR6, and CCR10 which direct the cells to barrier surfaces such as the skin and mucosal tissue.[3][5][6] Th22 cells are also associated with the release of chemokines CXCL1, CXCL5, and CXCL9, which are associated with the recruitment of other inflammatory cells to the area.[7]

IL-22 expression stimulates the growth of keratinocytes and epithelial cells, helping to maintain the innate barrier of skin and other organs.[7] Similarly, IL-22, the characteristic cytokine produced by Th22 cells has little effect on immune cells and instead acts on mucosal barriers.[5] Due to mucosal barrier interactions Th22 and subsequently IL-22 play a significant role in a variety of skin diseases, intestinal diseases, autoimmune diseases, and allergy conditions. Many of these diseases are characterized by increased circulation of Th22 cells and concomitant increased IL-22 expression.[3]

In psoriasis, there is a positive feedback loop between Th22 and IL-22 expression.[3] Increased expression of IL-22 is observed during lesion formation that augments the expression of anti-microbials and induces chemokine ligand (CCL)-20 recruiting CCR6, which is expressed on Th22 cells increasing their concentration in the lesion.[3] Similarly, Th22 cells are found throughout the intestinal wall in irritable bowel diseases, facilitating IL-22 secretion and subsequent induction of tissue specific genes.[3][8] Interestingly, Th22 cells induced expression of IL-22 in allergic asthma has been seen to have a protective effect against lung hypertension and tissue damage in murine models.[3]

References

  1. 1 2 Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H (August 2009). "Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells". Nature Immunology. 10 (8): 864–871. doi:10.1038/ni.1770. PMID 19578368. S2CID 30507460.
  2. ↑ Rothhammer V, Quintana FJ (March 2019). "The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease". Nature Reviews. Immunology. 19 (3): 184–197. doi:10.1038/s41577-019-0125-8. PMID 30718831. S2CID 59603271.
  3. 1 2 3 4 5 6 7 8 Jia L, Wu C (2014). "The Biology and Functions of Th22 Cells". In Sun B (ed.). T Helper Cell Differentiation and Their Function. Advances in Experimental Medicine and Biology. Vol. 841. Dordrecht: Springer Netherlands. pp. 209–230. doi:10.1007/978-94-017-9487-9_8. ISBN 978-94-017-9487-9. PMID 25261209.
  4. ↑ Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F (August 2009). "Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells". Nature Immunology. 10 (8): 857–863. doi:10.1038/ni.1767. PMID 19578369. S2CID 205362675.
  5. 1 2 3 Jiang Q, Yang G, Xiao F, Xie J, Wang S, Lu L, Cui D (2021). "Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases". Frontiers in Immunology. 12 688066. doi:10.3389/fimmu.2021.688066. PMC 8290841. PMID 34295334.
  6. ↑ Fard NA, Azizi G, Mirshafiey A (July 2016). "The Potential Role of T Helper Cell 22 and IL-22 in Immunopathogenesis of Multiple Sclerosis". Innovations in Clinical Neuroscience. 13 (7–8): 30–36. PMC 5022987. PMID 27672486.
  7. 1 2 Doulabi H, Masoumi E, Rastin M, Azarnaminy AF, Esmaeili SA, Mahmoudi M (January 2022). "The role of Th22 cells, from tissue repair to cancer progression". Cytokine. 149. doi:10.1016/j.cyto.2021.155749. PMID 34739898.
  8. ↑ Li LJ, Gong C, Zhao MH, Feng BS (December 2014). "Role of interleukin-22 in inflammatory bowel disease". World Journal of Gastroenterology. 20 (48): 18177–18188. doi:10.3748/wjg.v20.i48.18177. PMC 4277955. PMID 25561785.
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