Exploring the role of Janus kinase (JAK) in atopic dermatitis: a review of molecular mechanisms and therapeutic strategies

Figures & data

Figure 1. An overview of Janus kinase (JAK)-related cytokines. From the top, the coupled- receptor families, corresponding cytokines, combinations of JAKs, and coverage of subtypes of JAK inhibitors. INF: interferon, GM-CSF: Granulocyte-macrophage colony-stimulating factor, EPO: erythropoietin, TP: thrombopoietin.

Table 1. Pairs of Janus kinases (JAK) and corresponding cytokines. The table was modified from REF [11], which shows the cytokines expression downstream of a couple of JAKs in a permutational combinatorial manner. Notably, yellow-colored areas indicate homodimeric pairs of JAKs and exist at the table’s diagonal. In contrast, the pink-colored areas, which show a heterodimeric couple of JAKs, mirror the region of the orange-colored space from the diagonal lines. INF: interferon, GM-CSF: Granulocyte-macrophage colony-stimulating factor, EPO: erythropoietin, TP: thrombopoietin.

	JAK1	JAK2	JAK3	TYK2
JAK1	No dimerization	IFNγ, IL-6, IL-11, IL-13, TSLP	IL-2, IL-4, IL-7, IL-9, IL-13, IL-15, IL-21	IFNα, IFNβ, IL-10, IL-19, IL-20, IL-22, IL-6, IL-11, IL-13, IL-27, IL-31
JAK2	IFNγ, IL-6, IL-11, IL-13, TSLP	IL-3, IL-5, GM-CSF, EPO, TP	No dimerization	IL-12, IL-23
JAK3	IL-2, IL-4, IL-7, IL-9, IL-13, IL-15, IL-21	No dimerization	No dimerization	No dimerization
TYK2	IFNα, IFNβ, IL-10, IL-19, IL-20, IL-22, IL-6, IL-11, IL-13, IL-27, IL-31	IL-12, IL-23	No dimerization	No dimerization

Figure 2. Cytokine pathways in atopic dermatitis pathogenesis and molecular-targeted therapies. Note that JAK2-, JAK3-, and Tyk2-specific inhibitors whose coverages are indicated by dashed lines are not approved for AD treatment.

Garcia-Melendo C, Cubiró X, Puig L. Janus kinase inhibitors in dermatology: part 1—general considerations and applications in vitiligo and alopecia areata. Actas Dermo-Sifiliográficas (English Edition). 2021; 112(6):503–515.

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