Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant

Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant Publisher Pubmed

Boissondupuis S^{1, 2, 3} ; Ramirezalejo N¹ ; Li Z^{4, 5} ; Patin E^{6, 7, 8} ; Rao G⁹ ; Kerner G^{2, 3} ; Lim CK^{10, 11} ; Krementsov DN¹² ; Hernandez N¹ ; Ma CS^{9, 13} ; Zhang Q^{1, 14} ; Markle J¹ ; Martinezbarricarte R¹ ; Payne K⁹ Show All Authors

Boissondupuis S^{1, 2, 3}
Ramirezalejo N¹
Li Z^{4, 5}
Patin E^{6, 7, 8}
Rao G⁹
Kerner G^{2, 3}
Lim CK^{10, 11}
Krementsov DN¹²
Hernandez N¹
Ma CS^{9, 13}
Zhang Q^{1, 14}
Markle J¹
Martinezbarricarte R¹
Payne K⁹
Fisch R¹
Deswarte C^{2, 3}
Halpern J¹
Bouaziz M^{2, 3}
Mulwa J¹
Sivanesan D^{15, 16}
Lazarov T¹⁷
Naves R¹⁸
Garcia P¹⁹
Itan Y^{1, 20, 21}
Boisson B^{1, 2, 3}
Checchi A^{2, 3}
Jabothanin F^{2, 3}
Cobat A^{2, 3}
Guennoun A¹⁴
Jackson CC^{1, 22}
Pekcan S²³
Caliskaner Z²⁴
Inostroza J²⁵
Costacarvalho BT²⁶
Tavares De Albuquerque JA²⁷
Garciaortiz H²⁸
Orozco L²⁸
Ozcelik T²⁹
Abid A³⁰
Rhorfi IA^{30, 31}
Souhi H³⁰
Amrani HN³⁰
Zegmout A³⁰
Geissmann F¹⁷
Michnick SW¹⁵
Mullerfleckenstein I³¹
Fleckenstein B³¹
Puel A^{1, 2, 3}
Ciancanelli MJ¹
Marr N¹⁴
Abolhassani H^{10, 32}
Balcells ME³³
Condinoneto A²⁷
Strickler A³⁴
Abarca K³⁵
Teuscher C³⁶
Ochs HD³⁷
Reisli I³⁸
Sayar EH³⁸
Elbaghdadi J³⁹
Bustamante J^{1, 2, 3, 40}
Hammarstrom L^{10, 11, 41}
Tangye SG^{9, 13}
Pellegrini S^{4, 5}
Quintanamurci L^{6, 7, 8}
Abel L^{1, 2, 3}
Casanova JL^{1, 2, 3, 42, 43}

Show Affiliations

1. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, United States
2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France
3. Paris Descartes University, Imagine Institute, Paris, France
4. Cytokine Signaling Unit, Pasteur Institute, Paris, France
5. INSERM U1221, Paris, France
6. Human Evolutionary Genetics Unit, Pasteur Institute, Paris, France
7. CNRS UMR2000, Paris, France
8. Center of Bioinformatics, Biostatistics and Integrative Biology, Pasteur Institute, Paris, France
9. Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
10. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
11. Department of Clinical Translational Research, Singapore General Hospital, Singapore, Singapore
12. Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT, United States
13. St. Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, Australia
14. Sidra Medicine, Doha, Qatar
15. Department of Biochemistry, University of Montreal, Montreal, QC, Canada
16. Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada
17. Im-munology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, United States
18. Institute of Biochemical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
19. Laboratory of Microbiology, Clinical Laboratory Department School of Medicine, Pontifical Catholic University of Chile, Santiago, Chile
20. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States
21. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
22. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, United States
23. Department of Pediatric Pulmonology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey
24. Meram Faculty of Medicine, Department of Internal Medicine, Division of Allergy and Immunology, Necmettin Erbakan University, Konya, Turkey
25. Jeffrey Modell Center for Diagnosis and Research in Primary Immunodeficiencies, Faculty of Medicine University of La Frontera, Temuco, Chile
26. Department of Pediatrics, Federal University of Sao Paulo Medical School, Sao Paulo, Brazil
27. Department of Immunology, Institute of Biomedical Sciences, Institute of Tropical Medicine, University of Sao Paulo, Sao Paulo, Brazil
28. National Institute of Genomic Medicine, Mexico City, Mexico
29. Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey
30. Department of Pneumology, Military Hospital Mohammed V, Rabat, Morocco
31. Institute of Clinical and Molecular Virology, University of Erlangen-Nuremberg, Erlangen, Germany
32. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
33. Department of Infectious Diseases, Medical School, Pontifical Catholic University of Chile, Santiago, Chile
34. Department of Pediatrics, San Sebastian University, Santiago, Chile
35. Department of Infectious Diseases and Pediatric Immunology, School of Medicine, Pontifical Catholic University of Chile, Santiago, Chile
36. Department of Medicine, Immunobiology Program, University of Vermont, Burlington, VT, United States
37. Seattle Children's Research Institute, Department of Pediatrics, University of Washington, Seattle, WA, United States
38. Department of Pediatric Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey
39. Genetics Unit, Military Hospital Mohamed V, Hay Riad, Rabat, Morocco
40. Center for the Study of Primary Immunodeficiencies, AP-HP, Necker Hospital for Sick Children, Paris, France
41. Beijing Genomics Institute BGI-Shenzhen, Shenzhen, China
42. Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France
43. Howard Hughes Medical Institute, New York, NY, United States

Source: Science Immunology Published:2018

Abstract

Inherited IL-12R1 and TYK2 deficiencies impair both IL-12– and IL-23–dependent IFN- immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common TYK2 P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls (P = 8.37 × 10−8; odds ratio, 89.31; 95% CI, 14.7 to 1725). Moreover, the frequency of P1104A in Europeans has decreased, from about 9% to 4.2%, over the past 4000 years, consistent with purging of this variant by endemic tuberculosis. Surprisingly, we also show that TYK2 P1104A impairs cellular responses to IL-23, but not to IFN-, IL-10, or even IL-12, which, like IL-23, induces IFN- via activation of TYK2 and JAK2. Moreover, TYK2 P1104A is properly docked on cytokine receptors and can be phosphorylated by the proximal JAK, but lacks catalytic activity. Last, we show that the catalytic activity of TYK2 is essential for IL-23, but not IL-12, responses in cells expressing wild-type JAK2. In contrast, the catalytic activity of JAK2 is redundant for both IL-12 and IL-23 responses, because the catalytically inactive P1057A JAK2, which is also docked and phosphorylated, rescues signaling in cells expressing wild-type TYK2. In conclusion, homozygosity for the catalytically inactive P1104A missense variant of TYK2 selectively disrupts the induction of IFN- by IL-23 and is a common monogenic etiology of tuberculosis. Copyright © 2018 The Authors, some rights reserved.

Related Docs

View other Related Docs

1. Human Il-23 Is Essential for Ifn-Γ–Dependent Immunity to Mycobacteria, Science Immunology (2023)

2. Impaired Il-23–Dependent Induction of Ifn-Γ Underlies Mycobacterial Disease in Patients With Inherited Tyk2 Deficiency, Journal of Experimental Medicine (2022)

3. Inherited and Acquired Immunodeficiencies Underlying Tuberculosis in Childhood, Immunological Reviews (2015)

4. Human Mcts1-Dependent Translation of Jak2 Is Essential for Ifn-Γ Immunity to Mycobacteria, Cell (2023)

5. Primary Immunodeficiency Diseases and Bacillus Calmette-Guerin (Bcg)-Vaccine–Derived Complications: A Systematic Review, Journal of Allergy and Clinical Immunology: In Practice (2020)

6. Molecular, Immunological, and Clinical Features of 16 Iranian Patients With Mendelian Susceptibility to Mycobacterial Disease, Journal of Clinical Immunology (2019)

7. Inherited Human Itk Deficiency Impairs Ifn-Γ Immunity and Underlies Tuberculosis, Journal of Experimental Medicine (2023)

8. The Human Cib1-Ever1-Ever2 Complex Governs Keratinocyte-Intrinsic Immunity to Β-Papillomaviruses, Journal of Experimental Medicine (2018)

Experts (# of related papers)

View all Related Experts

Nima Rezaei (15)

Nima Parvaneh (13)

Style	Citing Format
MLA	Boissondupuis S, et al.. "Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant." Science Immunology, vol. 3, no. 30, 2018, pp. -.
APA	Boissondupuis S, Ramirezalejo N, Li Z, Patin E, Rao G, Kerner G, Lim CK, Krementsov DN, Hernandez N, Ma CS, Zhang Q, Markle J, Martinezbarricarte R, Payne K, Fisch R, Deswarte C, Halpern J, Bouaziz M, Mulwa J, ... Casanova JL (2018). Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant. Science Immunology, 3(30), -.
Chicago	Boissondupuis S, Ramirezalejo N, Li Z, Patin E, Rao G, Kerner G, Lim CK, et al.. "Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant." Science Immunology 3, no. 30 (2018): -.
Harvard	Boissondupuis S et al. (2018) 'Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant', Science Immunology, 3(30), pp. -.
Vancouver	Boissondupuis S, Ramirezalejo N, Li Z, Patin E, Rao G, Kerner G, et al.. Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant. Science Immunology. 2018;3(30):-.
BibTex	@article{ author = {Boissondupuis S and Ramirezalejo N and Li Z and Patin E and Rao G and Kerner G and Lim CK and Krementsov DN and Hernandez N and Ma CS and Zhang Q and Markle J and Martinezbarricarte R and Payne K and Fisch R and Deswarte C and Halpern J and Bouaziz M and Mulwa J and Sivanesan D and Lazarov T and Naves R and Garcia P and Itan Y and Boisson B and Checchi A and Jabothanin F and Cobat A and Guennoun A and Jackson CC and Pekcan S and Caliskaner Z and Inostroza J and Costacarvalho BT and Tavares De Albuquerque JA and Garciaortiz H and Orozco L and Ozcelik T and Abid A and Rhorfi IA and Souhi H and Amrani HN and Zegmout A and Geissmann F and Michnick SW and Mullerfleckenstein I and Fleckenstein B and Puel A and Ciancanelli MJ and Marr N and Abolhassani H and Balcells ME and Condinoneto A and Strickler A and Abarca K and Teuscher C and Ochs HD and Reisli I and Sayar EH and Elbaghdadi J and Bustamante J and Hammarstrom L and Tangye SG and Pellegrini S and Quintanamurci L and Abel L and Casanova JL}, title = {Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant}, journal = {Science Immunology}, volume = {3}, number = {30}, pages = {-}, year = {2018} }
RIS	TY - JOUR AU - Boissondupuis S AU - Ramirezalejo N AU - Li Z AU - Patin E AU - Rao G AU - Kerner G AU - Lim CK AU - Krementsov DN AU - Hernandez N AU - Ma CS AU - Zhang Q AU - Markle J AU - Martinezbarricarte R AU - Payne K AU - Fisch R AU - Deswarte C AU - Halpern J AU - Bouaziz M AU - Mulwa J AU - Sivanesan D AU - Lazarov T AU - Naves R AU - Garcia P AU - Itan Y AU - Boisson B AU - Checchi A AU - Jabothanin F AU - Cobat A AU - Guennoun A AU - Jackson CC AU - Pekcan S AU - Caliskaner Z AU - Inostroza J AU - Costacarvalho BT AU - Tavares De Albuquerque JA AU - Garciaortiz H AU - Orozco L AU - Ozcelik T AU - Abid A AU - Rhorfi IA AU - Souhi H AU - Amrani HN AU - Zegmout A AU - Geissmann F AU - Michnick SW AU - Mullerfleckenstein I AU - Fleckenstein B AU - Puel A AU - Ciancanelli MJ AU - Marr N AU - Abolhassani H AU - Balcells ME AU - Condinoneto A AU - Strickler A AU - Abarca K AU - Teuscher C AU - Ochs HD AU - Reisli I AU - Sayar EH AU - Elbaghdadi J AU - Bustamante J AU - Hammarstrom L AU - Tangye SG AU - Pellegrini S AU - Quintanamurci L AU - Abel L AU - Casanova JL TI - Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant JO - Science Immunology VL - 3 IS - 30 SP - EP - PY - 2018 ER -

Style

Citing Format

MLA

Boissondupuis S, et al.. "Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant." Science Immunology, vol. 3, no. 30, 2018, pp. -.

APA

Boissondupuis S, Ramirezalejo N, Li Z, Patin E, Rao G, Kerner G, Lim CK, Krementsov DN, Hernandez N, Ma CS, Zhang Q, Markle J, Martinezbarricarte R, Payne K, Fisch R, Deswarte C, Halpern J, Bouaziz M, Mulwa J, ... Casanova JL (2018). Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant. Science Immunology, 3(30), -.

Chicago

Boissondupuis S, Ramirezalejo N, Li Z, Patin E, Rao G, Kerner G, Lim CK, et al.. "Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant." Science Immunology 3, no. 30 (2018): -.

Harvard

Boissondupuis S et al. (2018) 'Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant', Science Immunology, 3(30), pp. -.

Vancouver

Boissondupuis S, Ramirezalejo N, Li Z, Patin E, Rao G, Kerner G, et al.. Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant. Science Immunology. 2018;3(30):-.

BibTex

@article{ author = {Boissondupuis S and Ramirezalejo N and Li Z and Patin E and Rao G and Kerner G and Lim CK and Krementsov DN and Hernandez N and Ma CS and Zhang Q and Markle J and Martinezbarricarte R and Payne K and Fisch R and Deswarte C and Halpern J and Bouaziz M and Mulwa J and Sivanesan D and Lazarov T and Naves R and Garcia P and Itan Y and Boisson B and Checchi A and Jabothanin F and Cobat A and Guennoun A and Jackson CC and Pekcan S and Caliskaner Z and Inostroza J and Costacarvalho BT and Tavares De Albuquerque JA and Garciaortiz H and Orozco L and Ozcelik T and Abid A and Rhorfi IA and Souhi H and Amrani HN and Zegmout A and Geissmann F and Michnick SW and Mullerfleckenstein I and Fleckenstein B and Puel A and Ciancanelli MJ and Marr N and Abolhassani H and Balcells ME and Condinoneto A and Strickler A and Abarca K and Teuscher C and Ochs HD and Reisli I and Sayar EH and Elbaghdadi J and Bustamante J and Hammarstrom L and Tangye SG and Pellegrini S and Quintanamurci L and Abel L and Casanova JL}, title = {Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant}, journal = {Science Immunology}, volume = {3}, number = {30}, pages = {-}, year = {2018} }

RIS

TY - JOUR
AU - Boissondupuis S
AU - Ramirezalejo N
AU - Li Z
AU - Patin E
AU - Rao G
AU - Kerner G
AU - Lim CK
AU - Krementsov DN
AU - Hernandez N
AU - Ma CS
AU - Zhang Q
AU - Markle J
AU - Martinezbarricarte R
AU - Payne K
AU - Fisch R
AU - Deswarte C
AU - Halpern J
AU - Bouaziz M
AU - Mulwa J
AU - Sivanesan D
AU - Lazarov T
AU - Naves R
AU - Garcia P
AU - Itan Y
AU - Boisson B
AU - Checchi A
AU - Jabothanin F
AU - Cobat A
AU - Guennoun A
AU - Jackson CC
AU - Pekcan S
AU - Caliskaner Z
AU - Inostroza J
AU - Costacarvalho BT
AU - Tavares De Albuquerque JA
AU - Garciaortiz H
AU - Orozco L
AU - Ozcelik T
AU - Abid A
AU - Rhorfi IA
AU - Souhi H
AU - Amrani HN
AU - Zegmout A
AU - Geissmann F
AU - Michnick SW
AU - Mullerfleckenstein I
AU - Fleckenstein B
AU - Puel A
AU - Ciancanelli MJ
AU - Marr N
AU - Abolhassani H
AU - Balcells ME
AU - Condinoneto A
AU - Strickler A
AU - Abarca K
AU - Teuscher C
AU - Ochs HD
AU - Reisli I
AU - Sayar EH
AU - Elbaghdadi J
AU - Bustamante J
AU - Hammarstrom L
AU - Tangye SG
AU - Pellegrini S
AU - Quintanamurci L
AU - Abel L
AU - Casanova JL
TI - Tuberculosis and Impaired Il-23–Dependent Ifn- Immunity in Humans Homozygous for a Common Tyk2 Missense Variant
JO - Science Immunology
VL - 3
IS - 30
SP -
EP -
PY - 2018
ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract