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Pathbreaking research is shedding light on the role of TYK2 in immunology

Certain immune-mediated diseases are characterized by the elevation of inflammatory cytokines regulated by several components. The tyrosine kinase 2 pathway plays a critical role in regulating certain triggers of inflammation involved in immune diseases.1,2

About TYK2

Know TYK2

Tyrosine kinase 2 (TYK2) is an intracellular enzyme involved in the relay of immune signals initiated by specific cytokines, including IL-23, IL-12 and Type I IFN.1,2

TYK2 is a central link between certain cytokines, such as IL-23, IL-12 and Type I IFN, and the downstream effects of these cytokines.3

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TYK2 and JAK2 graphic
TYK2 and JAK2 graphic

IL-23 signaling through TYK2/JAK2 is critical in the expansion and survival of pathogenic Th17 cells as well as the induction of innate lymphoid cells in autoimmunity.4-6


IL-12-induced TYK2/JAK2 activation initiates recruitment and phosphorylation of STAT4, which activates transcription of a major effector molecule in systemic immune disorders.4,5

IFNα, β

Activation by type I IFNs signaling through TYK2/JAK1 in the B cell impacts pathways important in autoimmunity such as B-cell differentiation, antibody production, and immunoglobulin isotype class switching.7

See the TYK2 pathway in action

TYK2 pathway video thumbnail


Understand the differences

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TYK2 and JAK1/2/3 are structurally different from each other8

The regulatory, or pseudokinase, domain of TYK2 and JAK1/2/3 are different from each other.8

TYK2 vs JAK protein graphic TYK2 vs JAK protein graphic

Active (ATP-binding) domain: similar across family members8

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TYK2 and JAK1/2/3 are functionally different from each other9,10

TYK2 and JAK1/2/3 proteins form different dimers to mediate different sets of cytokine signals that can influence immune and/or systemic responses.9,10

TYK2 pathways vs JAK1/2/3 pathway graphic

The TYK2 and JAK1/2 pairs specifically mediate signals involved in immune functions2,3,10

JAK/JAK pairs mediate signals predominantly involved in both immune and broad systemic functions (eg, blood cell development, lipid metabolism)9-13

*Please note that this list of cytokines and effects modulated by the different TYK2/JAK and JAK/JAK pairs is not exhaustive. Certain cytokines might also be modulated by JAK and TYK2 trimers.2

ATP=adenosine triphosphate; EPO=erythropoietin; GH=growth hormone; GM-CSF=granulocyte-macrophage colony-stimulating factor; IFN=interferon; IL=interleukin; JAK=Janus kinase; TPO=thrombopoietin; TYK2=tyrosine kinase 2.

Emerging science


At BMS, we are committed to helping patients prevail over serious immune-related diseases such as psoriasis. We’re excited about our innovative research on the TYK2 pathway and the role it may play in immunology.

Download the TYK2 Fact Sheet

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  1. Mahil SK, Capon F, Barker JN. Update on psoriasis immunopathogenesis and targeted immunotherapy. Semin Immunopathol. 2016;38(1):11-27. doi:10.1007/s00281-015-0539-8
  2. Baker KF, Isaacs JD. Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis? Ann Rheum Dis. 22018;77(2):175-187. doi:10.1136/annrheumdis-2017-211555
  3. Dendrou CA, Cortes A, Shipman L, et al. Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med. 2016;8:363ra149.
  4. Ishizaki M, Akimoto T, Muromoto R, et al. Involvement of tyrosine kinase-2 in both the IL-12/Th1 and IL-23/Th17 axes in vivo. J Immunol. 2011;187(1):181-189. doi:10.4049/jimmunol.1003244
  5. Paunović V, Carroll HP, Vandenbroeck K, Gadina M. Signalling, inflammation and arthritis: crossed signals: the role of interleukin (IL)-12, -17, -23 and -27 in autoimmunity. Rheumatology (Oxford). 2008;47(6):771-776. doi:10.1093/rheumatology/kem352
  6. Geremia A, Arancibia-Cárcamo CV, Fleming MPP, et al. IL-23—responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med. 2011;208(6):1127-1133. doi:10.1084/jem.20101712
  7. Rönnblom L, Eloranta ML, Alm GV. The type I interferon system in systemic lupus erythematosus. Arthritis Rheum. 2006;54(2):408-420. doi:10.1002/art.21571
  8. Tokarski JS, Zupa-Fernandez A, Tredup JA, et al. Tyrosine kinase 2-mediated signal transduction in T lymphocytes is blocked by pharmacological stabilization of its pseudokinase domain. J Biol Chem. 2015;290(17):11061-11074. doi:10.1074/jbc.M114.619502
  9. Hammarén HM, Virtanen AT, Raivola J, Silvennoinen O. The regulation of JAKs in cytokine signaling and its breakdown in disease. Cytokine. 2019;118:48-63.
  10. Morris R, Kershaw NJ, Babon JJ. The molecular details of cytokine signaling via the JAK/STAT pathway. Protein Sci. 2018;27:1984-2009. doi:10.1002/pro.3519
  11. Xu D, Yin C, Wang S, Xiao Y. JAK-STAT in lipid metabolism of adipocytes. JAKSTAT. 2013;2(4):e27203. doi:10.4161/jkst.27203
  12. Jiang L, Li Z, Rui L. Leptin stimulates both JAK2-dependent and JAK2-independent signaling pathways. J Biol Chem. 2008;283:28066-28073. doi:10.1074/jbc.M805545200
  13. Richard AJ, Stephens JM. Emerging roles of JAK-STAT signaling pathways in adipocytes. Trends Endocrinol Metab. 2011;22:325-332.