Disease relevance of IL17D

• Commensal Gram-negative bacteria prime human dendritic cells for enhanced IL-23 and IL-27 expression and enhanced Th1 development [1].
• Thus, IL-27/WSX-1 affects the early development of EAU, and might be a target for therapy during the onset of autoimmune uveitis in humans [2].
• These data demonstrate a novel cytokine expressed by IL-17-producing T cells, and suggest interaction and synergy of IL-22 and IL-17 signaling pathways in tissue inflammation and autoimmune diseases [3].

High impact information on IL17D

• In this issue of Immunity, IL-27 is described, which acts in synergy with IL-12 early in Th1 development from naive T cells via the receptor TCCR/WSX-1 [4].
• We further demonstrate that IL-22 was coexpressed in vitro and in vivo with both IL-17A and IL-17F [5].
• To study a functional relationship among these cytokines, we examined the expression of antimicrobial peptides by primary keratinocytes treated with combinations of IL-22, IL-17A, and IL-17F [5].
• The subsequent expansion of IL-22-producing cells was dependent on IL-23 [5].
• We demonstrate that Th17 cells also expressed IL-22, an IL-10 family member, at substantially higher amounts than T helper (Th)1 or Th2 cells [5].

Biological context of IL17D

• Collectively, we have identified IL-22 as a new cytokine expressed by Th17 cells that synergizes with IL-17A or IL-17F to regulate genes associated with skin innate immunity [5].
• The structural composition of these genes shows two introns and three exons except for IL-17D gene that has only one intron and two exons [6].

Anatomical context of IL17D

• IL-17D is preferentially expressed in skeletal muscle, brain, adipose tissue, heart, lung, and pancreas [7].
• The EBV-induced gene 3 (EBI3) is expressed in dendritic cells (DCs) and part of the cytokine IL-27 that controls Th cell development [8].
• CONCLUSION: These data suggest that IL-22, produced by synovial fibroblasts and macrophages, promotes inflammatory responses in RA synovial tissues by inducing the proliferation and chemokine production of synovial fibroblasts [9].
• When present on antigen presenting cells, Necl2 regulates IL-22 expression by activated CD8(+) T-cells [10].
• RESULTS: IL-22 messenger RNA was detected by RT-PCR in RA synovial tissues and mononuclear cells isolated from RA synovial fluid samples [9].

Regulatory relationships of IL17D

• For example, the discovery of IL-27 has greatly improved our understanding of the factors regulating the polarization of the T helper cell responses and IL-31 appears to be an important regulator of Th2 responses [11].

Other interactions of IL17D

• Similar to IL-17A, IL-22 expression was initiated by transforming growth factor beta signaling in the context of IL-6 and other proinflammatory cytokines [5].

Analytical, diagnostic and therapeutic context of IL17D

• A novel cytokine termed IL-17D was cloned using nested RACE PCR [7].
• METHODS: Expression of IL-22 and IL-22 receptor 1 (IL-22R1) was examined by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis [9].
• Expression of IL-22 and IL-22R1 in RASF was confirmed by RT-PCR and Western blot analysis [9].
• IL-22 and IL-17 were found to be coordinately regulated by TGFbeta and IL-6 during TH differentiation by real-time PCR as well as ELISA analysis [3].

References