IL12IL23

IL-12 and IL-23 are cytokines in the interleukin-12 family. They are heterodimeric proteins that share a common p40 subunit; IL-12 consists of p35 and p40, while IL-23 consists of p19 and p40. They are produced primarily by antigen-presenting cells such as dendritic cells, macrophages, and monocytes in response to microbial products and inflammatory stimuli.

Receptors and signaling: IL-12 signals through a receptor composed of IL-12Rβ1 and IL-12Rβ2 and activates the JAK-STAT pathway, particularly STAT4. IL-23 signals through IL-23R and IL-12Rβ1 and activates STAT3 (with some involvement of other STAT proteins). This shared receptor subunit basis explains overlapping but distinct roles in immune responses.

Biological roles: IL-12 promotes differentiation of naive CD4+ T cells into Th1 cells and stimulates production of IFN-γ, enhancing cell-mediated immunity against intracellular pathogens. IL-23 supports the expansion and maintenance of Th17 cells and drives IL-17 production, contributing to neutrophil recruitment and inflammatory responses. Together, they coordinate innate and adaptive immune responses and help shape T helper cell phenotypes.

Clinical significance: Dysregulation of the IL-12/IL-23 axis has been implicated in autoimmune and inflammatory diseases, including psoriasis, psoriatic arthritis, inflammatory bowel disease, and other chronic inflammatory conditions. Therapeutic strategies have targeted this axis, notably ustekinumab, a monoclonal antibody against the p40 subunit shared by IL-12 and IL-23, as well as p19-specific antibodies that selectively inhibit IL-23.

Notes: The cytokines are part of a broader IL-12 family and illustrate the balance between protective immunity and inflammatory pathology.

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