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IL-12 and IL-23

Interleukin-12 (IL-12):

 Structure: Heterodimeric cytokine composed of p35 and p40 subunits

Mainly produced by: Dendritic cells, macrophages, neutrophils

Promotes differentiation of naive T cells into Th1 cells

 Enhances the cytotoxic activity of NK cells and CD8+ T cells

 Stimulates IFN-γ production

 Role in immunity: Critical for cell-mediated immunity against intracellular pathogens

Interleukin-23 (IL-23):

 Heterodimeric cytokine composed of p19 and p40 subunits (shares p40 with IL-12)

  Produced by activated dendritic cells and macrophages

   Promotes differentiation and maintenance of Th17 cells

  Stimulates production of IL-17, IL-22, and TNF-α

  Important for mucosal immunity and inflammation

  Both are members of the IL-12 family of cytokines

  Share the p40 subunit but have distinct biological activities

  IL-12 primarily drives Th1 responses, while IL-23 promotes Th17 responses

  Dysregulation of IL-12 and IL-23 is implicated in various autoimmune and inflammatory disorders.

 Therapeutic targeting of these cytokines has shown promise in treating conditions like psoriasis, inflammatory bowel disease, and rheumatoid arthritis.

The IL-12 and IL-23 cytokines play a critical role in homeostasis and inflammation in the intestinal tract.

They share various features, including a common 

 p40 cytokine  subunit, a common interleukin12 R receptor sub unit and Manus Kinase  signal transducer and activator of transcription(STAT) signaling molecule that communicates downstream functions.

Drugs that inhibited either the shared interleukin– 12  p40 sub unit or the selective interleukin 23 p19 subunit are utilized for treatment for Crohn’s disease

Interleukin-12 is involved in the differentiation of T cells to Th1 cells which are increased in Crohn’s disease: its inhibition, therefore reduces level of intestinal Th1 cells and reduces inflammation.

Interleukin12 p40 also associates with Interleukin 23 p19 to form interleukin 23 which expands and maintains Th17 cells.

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