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About the IL-23 Pathway

Shared Cytokines Across the Autoimmune Axis1-15

Shared Cytokines Across the Autoimmune Axis

Note: This is not intended to be a complete depiction of cells and cytokines possibly contributing to immune-mediated inflammatory conditions.
*Other cytokines that facilitate differentiation of Th17 cells include TGF-β, IL-1, and IL-6, while IL-23 promotes survival and expansion of the Th17 cells.12,13

ILC3=group 3 innate lymphoid cells; iNKT=invariant natural killer T cells; MAIT=mucosal-associated invariant T cells.

References: 
  1.  Boyapati R, et al. F1000 Prime Reports. 2015;7:44.
  2.  Szilagyi A. Clin J Gastroenterol. 2020;13(2):139-152.
  3.  Swanson GR, et al. Alcohol. 2010;44(3):223-228.
  4.  Chandra S, Kronenberg M. Advances in Immunology. 2015;127:145-201.
  5.  Chen F, et al. J Immunol. 2016;196(10):4390-4399.
  6.  Tecchio C, et al. Front Immunol. 2014;5:508.
  7.  De Winter BY, et al. Biochimica et Biophysica Acta. 2012;1822(1):66-73.
  8.  Scher J. J Rheumatol. 2018;94:32-35.
  9.  Scher J, et al. Arthritis Rheumatol. 2015;67(1):128-139.
  10.  Manasson J, et al. Arthritis Rheumatol. 2020;72(4):645-657.
  11.  Maillet J, et al. Joint Bone Spine. 2016;83(6):665-668.
  12.  Boutet MA, et al. Int J Mol Sci. 2018;19(2):530.
  13.  Eken A, Oukka M. Interleukin 23 in IBD Pathogenesis. New Insights into Inflammatory Bowel Disease. 2016. IntechOpen.
  14.  Gracey E, et al. Curr Opin Rheumatol. 2019;31(1):62-69.
  15.  Toussirot E, Saas P. RMD Open. 2018;4(2):e000821.

Regulatory Cytokines of Th1 and Th17 Pathways1-4

Regulatory Cytokines of Th1 and Th17 Pathways
References: 
  1.  Boutet MA, et al. Int J Mol Sci. 2018;19(2):530.
  2.  Hawkes JE, et al. J Immunol. 2018;201(6):1605-1613.
  3.  Eken A, Oukka M. Interleukin 23 in IBD Pathogenesis. New Insights into Inflammatory Bowel Disease. 2016. IntechOpen. doi:10.5772/64882.
  4.  Blanco P, et al. Cytokine Growth Factor Rev. 2008;19(1):41-52.

Podcast

Learn More About the IL-23, Th1, and Th17 Pathways With Dr. Jonathan Sherlock

Hello. Thank you very much for having me today and this opportunity to speak about inflammatory cytokines, particularly IL-23 and the way IL-23 coordinates inflammation around the body.

IL-23/Th17 in Plaque Psoriasis (PsO)

Plaque Psoriasis (PsO)

PsO Overview and Comorbidities

PsO Overview and Comorbidities
PsO has similar prevalence in males and females2
15-30 years (common age range at PsO onset)2

Comorbidities1,3:

PsA

IBD

(Crohn’s disease or ulcerative colitis)

Depression/
anxiety

Uveitis

Cardiovascular

CVD, hypertension, dyslipidemia

Metabolic

Obesity, insulin resistance, diabetes

NAFLD

CVD=cardiovascular disease; IBD=inflammatory bowel disease; NAFLD=non-alcoholic fatty liver disease; PsA=psoriatic arthritis.

References: 
  1.  Elmets CA, et al. J Am Acad Dermatol. 2019;80(4):1073-1113.
  2.  Weigle N, McBane S. Am Fam Physician. 2013;87(9):626-633.
  3.  Egeberg A, et al. Br J Dermatol. 2016;175(3):487-492.

IL-23 Drives Production of Pathogenic 
Th17 Cells in PsO1-17

IL-23 Drives Production of Pathogenic Th17 Cells in PsO

NOTE: This is not intended to be a complete depiction of cells and cytokines possibly contributing to psoriasis.
*Other cytokines that facilitate differentiation of Th17 cells include TGF-β, IL-1, and IL-6, while IL-23 promotes survival and expansion of Th17 cells.18,19

ILC3=group 3 innate lymphoid cells; iNKT=invariant natural killer T cells; MAIT=mucosal-associated invariant T cells.

References: 
  1.  Cua DJ, Sherlock JP. Nat Med. 2011;17(9):1055-1056.
  2.  Lories RJ, et al. Nat Med. 2012;18(7):1018-1019.
  3.  Haroon M, et al. Ann Rheum Dis. 2016;75(1):155-162.
  4.  Cuthbert R, et al. Arthritis Rheumatol. 2017;69(9):1816-1822.
  5.  Rizzo A, et al. Front Med. 2018;5:63.
  6.  Toussirot E, Saas P. RMD Open. 2018;4(2):e000821.
  7.  Raychaudhuri SK, et al. Cytokine. 2020;125:154855.
  8.  De Winter BY, et al. Biochimica et Biophysica Acta. 2012;1822(1):66-73.
  9.  Gracey E, et al. Curr Opin Rheumatol. 2019;31(1):62-69.
  10.  Lynde CW, et al. J Am Acad Dermatol. 2014;71:141-150.
  11.  Yip KH, et al. Sem Immunopath. 2019;41:401-410.
  12.  Tett A, et al. NPJ Biofilms Microbiomes. 2017;3:14. doi:10.1038/s41522-017-0022-5
  13.  Gracey E, et al. Curr Opin Rheumatol. 2019;31(1):62-69.
  14.  Codoñer FM, et al. Sci Rep. 2018;8(1):3812. doi:10.1038/s41598-018-22125-y
  15.  Airley RE, et al. Pharm J. 2000;264(7094):666-673.
  16.  Fyhrquist N, et al. Nat Commun. 2019;10(1):4703. doi:10.1038/s41467-019-12253-y
  17.  Lowes MA, et al. Annu Rev Immunol. 2014;32:227-255.
  18.  Boutet MA, et al. Int J Mol Sci. 2018;19(2):530. doi:10.3390/ijms19020530
  19.  Eken A, Oukka M. Interleukin 23 in IBD Pathogenesis. In: Huber S, ed. New Insights into Inflammatory Bowel Disease. IntechOpen; 2016. doi:10.5772/64882
IL-23/Th17 in Psoriatic Arthritis (PsA)

Psoriatic Arthritis (PsA)

PsA: A Complex, Heterogeneous Disease

pso map
Similar prevalence in males and females3
30-50 years (typical age of onset)4

PsA Domains:

More than 90% skin disease1
Up to 95% peripheral arthritis5
Up to 68% nail disease6
Up to 32% axial disease7*
Up to 40% enthesitis7
Up to 50% dactylitis7

*Based on an observational cohort at the University of Toronto PsA Clinic; registry currently includes 1066 registrants.

PsA: Common Comorbidities8,9

Uveitis

(possible extra-articular manifestation of the disease)

Depression/
Anxiety

IBD

(Crohn’s disease or ulcerative colitis; possibly extra-articular manifestation of the disease)

Cardiovascular

CVD, hypertension, dyslipidemia

Metabolic

Obesity, insulin resistance, diabetes

NAFLD

CVD=cardiovascular disease; IBD=inflammatory bowel disease; NAFLD=non-alcoholic fatty liver disease.

References: 
  1.  Mease P, Armstrong A. Drugs. 2014;75:423-441.
  2.  Mease PJ, et al. J Am Acad Dermatol. 2013;69(5):729-735.
  3.  Arthritis Foundation. Psoriatic Arthritis. https://arthritis.org/getmedia/a7d5903d-2f05-435f-8a75-1d0155d76edf/psoriatic-arthritis-brochure_better-living-toolkit_6-17-19.pdf. Accessed February 20, 2021.
  4.  Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/psoriatic-arthritis/symptoms-causes/syc-20354076. Accessed February 20, 2021.
  5.  Cho HH, Kim BS. J Lifestyle Med. 2013;3(2):85-90.
  6.  Zenke Y, et al. J Am Acad Dermatol. 2017;77:863-867.
  7.  Gladman DD, Chandran V. Rheumatology. 2011;50:25-31.
  8.  Coates LC, et al. Arthritis Rheumatol. 2016; doi10.2010/art.39573.
  9.  Ogdie A, Weiss P. Rheum Dis Clin North Am. 2015;41(4):545-568.

IL-23 Drives Production of Pathogenic 
Th17 Cells in PsA1-11

Gut Microbiota in the Development of PsA

NOTE: This is not intended to be a complete depiction of cells and cytokines possibly contributing to PsA.
*Other cytokines that facilitate differentiation of Th17 cells include TGF-β, IL-1, and IL-6, while IL-23 promotes survival and expansion of Th17 cells.12,13

AS=ankylosing spondylitis; ILC3=group 3 innate lymphoid cells; iNKT=invariant natural killer T cells; MAIT=mucosal-associated invariant T cells.

References: 
  1.  Laurence M, et al. Front Med. 2018;5:80.
  2.  Toussirot E, Saas P. RMD Open. 2018;4(2):e000821.
  3.  Chandra S, Kronenberg M. Adv Immunol. 2015;127:145-201.
  4.  Chen F, et al. J Immunol. 2016;196(10):4390-4399.
  5.  Tecchio C, et al. Front Immunol. 2014;5:508.
  6.  De Winter BY, et al. Biochimica et Biophysica Acta. 2012;1822(1):66-73.
  7.  Scher J. J Rheumatol. 2018;94:32-35.
  8.  Scher J, et al. Arthritis Rheumatol. 2015;67(1):128-139.
  9.  Manasson J, et al. Arthritis Rheumatol. 2020;72(4):645-657.
  10.  Maillet J, et al. Joint Bone Spine. 2016;83(6):665-668.
  11.  Gracey E, et al. Curr Opin Rheumatol. 2019;31(1):62-69.
  12.  Boutet MA, et al. Int J Mol Sci. 2018;19(2):530.
  13.  Eken A, Oukka M. 2016. IntechOpen.

IL-23 Drives Production of Pathogenic 
Th17 Cells in PsA1-9

*Mucosal-associated invariant T (MAIT) cells, γδT cells, and innate lymphoid cells of group 3 (ILC3).

ILC=innate lymphoid cell.

References: 
  1.  Cua DJ, Sherlock JP. Nat Med. 2011;17(9):1055-1056.
  2.  Lories RJ, et al. Nature Medicine. 2012;18(7):1018-1019.
  3.  Haroon M, et al. Ann Rheum Dis. 2016;75(1):155-162.
  4.  Cuthbert R, et al. Arthritis Rheumatol. 2017;69(9):1816-1822.
  5.  Rizzo A, et al. Front Med. 2018;5:63.
  6.  Toussirot E, Saas P. RMD Open. 2018;4(2):e000821.
  7.  Raychaudhuri SK, et al. Cytokine. 2020;125:154855.
  8.  De Winter BY, et al. Biochimica et Biophysica Acta. 2012;1822(1):66-73.
  9.  Gracey E, et al. Curr Opin Rheumatol. 2019;31(1):62-69.
IL-23/Th17 in Inflammatory Bowel Disease (IBD)

IL-23/Th17 in inflammatory bowel disease (IBD)

IBD Overview and EIM/Comorbidities

IBD Overview and EIM/Comorbidities
Similar prevalence in males and females4
20-30 years (CD); 30-40 years (UC)5

EIM and/or Comorbidities2,3:

Arthritis

Axial and/or peripheral

Psoriasis

Uveitis

Depression/
anxiety

Cardiovascular

CVD, hypertension, dyslipidemia

Metabolic

Obesity, insulin resistance, diabetes

Liver

Primary sclerosing cholangitis, NAFLD

CD=Crohn’s disease; CVD=cardiovascular disease; EIM=extraintestinal manifestations; NAFLD=non-alcoholic fatty liver disease; UC=ulcerative colitis.

References: 
  1.  CDC. https://www.cdc.gov/ibd/data-statistics.htm. Accessed December 13, 2019.
  2.  San Roman AL, Munoz F. World J Gastroenterol. 2011;17(22):2723-2733.
  3.  Argollo M, et al. Lancet Gastroenterol Hepatol. 2019;4(8):643-654.
  4.  Crohn’s and Colitis Foundation. IBD Factbook. https://www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated%20IBD%20Factbook.pdf. Accessed January 23, 2020.
  5.  Cosnes J, et al. Gastroenterology. 2011;140(6):1785-1794. doi:10.1053/j.gastro.2011.01.055.

IL-23 Drives Production of Pathogenic 
Th17 Cells in IBD1-19

IL-23 Drives Production of Pathogenic Th17 Cells in PsO

NOTE: This is not intended to be a complete depiction of cells and cytokines possibly contributing to IBD.

*Other cytokines that facilitate differentiation of Th17 cells include TGF-β, IL-1, and IL-6, while IL-23 promotes survival and expansion of Th17 cells.20,21

†Smoking has been associated with an increased risk in the development and severity of Crohn's disease.22

IBD=inflammatory bowel disease; ILC3=group 3 innate lymphoid cells; iNKT=invariant natural killer T cells; MAIT=mucosal-associated invariant T cells.

References: 
  1.  Airley RE, et al. Pharm J. 2000;264(7094):666-673.
  2.  Szilagyi A. Clin J Gastroenterol. 2019. doi:10.1007/s12328-019-01037-y.
  3.  Chandra S, Kronenberg M. Adv Immunol. 2015;127:145-201.
  4.  Chen F, et al. J Immunol. 2016;196(10):4390-4399.
  5.  Tecchio C, et al. Front Immunol. 2014;5:50B. doi: 10.3389/fimmu.2014.00508.
  6.  De Winter BY, et al. Biochimica et Biophysica Acta. 2012;1822:66-73.
  7.  Neurath M. Nature Reviews. 2014;14:329-342.
  8.  Boyapati R, et al. F1000 Prime Reports. 2015;7:1-18.
  9.  Dave M, et al. Gastroenterol Clin N Am. 2014;43:405-424.
  10.  Lam S, et al. AP&T. 2019;50:1159-1171.
  11.  Ni J, et al. Nat Rev Gastroenterol Hepatol. 2017;14(10):573-584.
  12.  Lee JS, et al. Immunity. 2015;43:727-738.
  13.  Gracey E, et al. Curr Opin Rheumatol. 2019;31:62-69.
  14.  Maloy KJ, Powrie F. Nature. 2011;474(7351):298-306.
  15.  Manasson J, et al. Arthritis Rheumatol. 2019; doi:10.1002/art.41169.
  16.  Swanson GR, et al. Alcohol. 2010;44(3):223–228.
  17.  Mortier C, et al. Front Immunol. 2018;9:1489. doi:10.3389/fimmu.2018.01489.
  18.  Castleman MJ, et al. Front Immunol. 2019;10:649.doi:10.3389/fimmu.2019.00649.
  19.  Blanco P, et al. Cytokine Growth Factor Rev. 2008;19(1):41-52.
  20.  Boutet MA, et al. Int J Mol Sci. 2018;19:530. doi:10.3390/ijms19020530.
  21.  Eken A, Oukka M. Interleukin 23 in IBD Pathogenesis. New Insights into Inflammatory Bowel Disease. 2016. IntechOpen. doi:10.5772/64882.
  22.  Nos P, Domenech E. World J Gastroenterol. 2011;17(31):3567-3574.
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