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General and
Specific Signaling
Pathways
Relating to
Type 2 Inflammation

The effects mediated by IL-4, IL-13, and IL-5 are specific to the Type 2 inflammatory cascade.1,2 In contrast, Jaks are an integral part of multiple pathways—and, as such, mediate signaling of several Jak-dependent cytokines that include, but are not limited to, those involved in Type 2 inflammation.3

Jak-signaling pathways:
The broad effect of
Jak enzymes3,4

Kinases involved in Jak pathways include Jak1, Jak2, Jak3, and Tyk2.3
IL-4, IL-13, and IL-5 represent Type 2 inflammatory pathways.1 Other cytokines represent different pathways outside of the Type 2 cascade.3

Jak-dependent cytokines are associated with a variety of immunoregulatory (physiologic) effects, such as3:

  • Antiviral response

  • Autoimmune response (via IL-6 signaling and others)

  • Hematopoiesis (blood cell formation)

  • Type 2 immune response (via IL-4, IL-13, and IL-5 signaling)

    • The Type 2 immune response can protect against helminth infections.2 When the Type 2 immune response is overactive, Type 2 cytokines are overproduced and Type 2 inflammation occurs1

Jak enzymes are more general than Type 2 cytokines, mediating a broad set of effects in addition to Type 2 inflammation.3,4

Type 2 Cytokines in
Different Diseases

Learn more

Barrier Dysfunction
in Different Diseases

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Epo=erythropoietin; G-CSF=granulocyte colony-stimulating factor; GH=growth hormone; GM-CSF=granulocyte-macrophage colony-stimulating factor; IFN=interferon; IL=interleukin; Jak=Janus kinase; LIF=leukemia inhibitory factor; OSM=oncostatin M; Tpo=thrombopoietin; Tyk=tyrosine kinase.

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References

  1. Gandhi NA, Bennett BL, Graham NM, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of Type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.

  2. Robinson D, Humbert M, Buhl R, et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161-175.

  3. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O’Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;17(1):78. doi:10.1038/nrd.2017.267

  4. Howell MD, Kuo FI, Smith PA. Targeting the Janus kinase family in autoimmune skin diseases. Front Immunol. 2019;10:2342. doi:10.3389/fimmu.2019.02342

IMM.20.10.0003 Last Update: [12/20]

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