Newly identified T helper cell 22 (Th22) is a subset of CD4+ T cells with specific properties apart from other known CD4+ T cell subsets. Th22 is obviously discrete from Th17 and Th1 subsets by production of interleukin (IL)-22 but not IL-17 or IFN-γ, and also with distinguished expression of aryl hydrocarbon receptor (AHR) as the key transcription factor. This T helper subset, by producing pro-inflammatory cytokines such as IL-22 and tumor necrosis factor-α (TNF-α), is implicated in the pathogenesis of inflammatory and autoimmune disorder. This review discusses the role of Th22 and its cytokine IL-22 in the immunopathogenesis of autoimmune disease including acute coronary syndrome, psoriasis, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, Behçet’s disease, type 1 and 2 diabetes and immune thrombocytopenia.
Th22 could almost be subsumed under the dominant Th17, just as Th9 could have been under Th2. But they are distinct: Th22 cells do not produce Th17, just as Th9 cells do not enumerate IL4; among other differences like cell surface markers.
What is more clinically relevant is their distinct contributions to host defence in health, and pathogenesis in disease. While Th9 evidently plays a key role in the pathogenesis of... Psoriatic Arthritis, Th22 cells were preferentially distributed in psoriatic skin in contrast to psoriatic synovium.
As our understanding of the biology of the newer T-helper subsets (Th9 and Th22) improve, it may help us understand why treatments like Secukinumab and Ustekinumab used in the treatment of broadly Th17-mediated diseases can result in surprisingly divergent effects.
Psoriasis is not "forme fruste" Psoriatic Arthritis, neither is Ulcerative Colitis "limited" Crohn's Disease. Th22 and Th9 may be nuancing Th1, Th2 and Th17 to differentiate these phenotypes.