M. Parkes, A. Cortes, D. A. Van-heel, and M. A. Brown, Genetic insights into common pathways and complex relationships among immune-mediated diseases, Nat Rev Genet, vol.14, issue.9, pp.661-73, 2013.

K. Papp, K. Gordon, D. Thaci, A. Morita, M. Gooderham et al., Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis, N Engl J Med, vol.379, issue.14, pp.1313-1334, 2018.

B. Strobl, D. Stoiber, V. Sexl, and M. Mueller, Tyrosine kinase 2 (TYK2) in cytokine signalling and host immunity, Front Biosci, vol.17, pp.3214-3246, 2011.

N. R. Leitner, A. Witalisz-siepracka, B. Strobl, and M. Muller, Tyrosine kinase 2-Surveillant of tumours and bona fide oncogene, Cytokine, vol.89, pp.209-227, 2017.

Z. Li, M. Gakovic, J. Ragimbeau, M. L. Eloranta, L. Ronnblom et al., Two rare disease-associated tyk2 variants are catalytically impaired but signaling competent, J Immunol, vol.190, issue.5, pp.2335-2379, 2013.
URL : https://hal.archives-ouvertes.fr/pasteur-02071008

C. A. Dendrou, A. Cortes, L. Shipman, H. G. Evans, K. E. Attfield et al., Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity, Sci Transl Med, vol.8, issue.363, pp.363-149, 2016.

S. Boisson-dupuis, N. Ramirez-alejo, Z. Li, P. E. Rao, G. Kerner et al., Tuberculosis and impaired IL-23-dependent IFN-gamma immunity in humans homozygous for a common TYK2 missense variant, Sci Immunol, vol.3, issue.30, 2018.

G. Kerner, N. Ramirez-alejo, Y. Seeleuthner, R. Yang, M. Ogishi et al., Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry, Proc Natl Acad Sci U S A, vol.116, issue.21, pp.10430-10434, 2019.
URL : https://hal.archives-ouvertes.fr/hal-02353025

J. A. Gorman, C. Hundhausen, M. Kinsman, T. Arkatkar, E. J. Allenspach et al., The TYK2-P1104A Autoimmune Protective Variant Limits Coordinate Signals Required to Generate Specialized T Cell Subsets, Front Immunol, vol.10, p.44, 2019.

C. Enerback, C. Sandin, S. Lambert, M. Zawistowski, P. E. Stuart et al., The psoriasis-protective TYK2 I684S variant impairs IL-12 stimulated pSTAT4 response in skin-homing CD4+ and CD8+ memory T-cells, Sci Rep, vol.8, issue.1, p.29728633, 2018.

D. S. Graham, M. Akil, and T. J. Vyse, Association of polymorphisms across the tyrosine kinase gene, TYK2 in UK SLE families, Rheumatology, vol.46, issue.6, pp.927-957, 2007.

A. Hellquist, T. M. Jarvinen, S. Koskenmies, M. Zucchelli, C. Orsmark-pietras et al., Evidence for Genetic Association and Interaction Between the TYK2 and IRF5 Genes in Systemic Lupus Erythematosus, J Rheumatol, vol.36, issue.8, pp.1631-1639, 2009.

S. Sigurdsson, G. Nordmark, H. H. Goring, K. Lindroos, A. C. Wiman et al., Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus, Am J Hum Genet, vol.76, issue.3, pp.528-565, 2005.

D. L. Morris, Y. Sheng, Y. Zhang, Y. F. Wang, Z. Zhu et al., Genome-wide association metaanalysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus, Nat Genet, vol.48, issue.8, pp.940-946, 2016.

C. Wallace, D. J. Smyth, M. Maisuria-armer, N. M. Walker, J. A. Todd et al., The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes, Nat Genet, vol.42, issue.1, pp.68-71, 2010.

J. Ragimbeau, E. Dondi, A. Alcover, P. Eid, G. Uze et al., The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression, EMBO J, vol.22, issue.3, pp.537-584, 2003.

A. Y. Kreins, M. J. Ciancanelli, S. Okada, X. F. Kong, N. Ramirez-alejo et al., Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome, J Exp Med, vol.212, issue.10, pp.1641-62, 2015.

S. Pellegrini, J. John, M. Shearer, I. M. Kerr, and G. R. Stark, Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway, Mol Cell Biol, vol.9, issue.11, pp.4605-4617, 1989.

M. C. Gauzzi, L. Velazquez, R. Mckendry, K. E. Mogensen, M. Fellous et al., Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase, J Biol Chem, vol.271, issue.34, pp.20494-500, 1996.
URL : https://hal.archives-ouvertes.fr/hal-02194141

G. S. Wang and T. A. Cooper, Splicing in disease: disruption of the splicing code and the decoding machinery, Nat Rev Genet, vol.8, issue.10, pp.749-61, 2007.

J. Ragimbeau, E. Dondi, A. Vasserot, P. Romero, G. Uze et al., The receptor interaction region of Tyk2 contains a motif required for its nuclear localization, J Biol Chem, vol.276, issue.33, pp.30812-30820, 2001.

M. F. Richter, G. Dumenil, G. Uze, M. Fellous, and S. Pellegrini, Specific contribution of Tyk2 JH regions to the binding and the expression of the interferon alpha/beta receptor component IFNAR1, J Biol Chem, vol.273, issue.38, pp.24723-24732, 1998.
URL : https://hal.archives-ouvertes.fr/hal-02196867

H. J. Wallweber, C. Tam, Y. Franke, M. A. Starovasnik, and P. J. Lupardus, Structural basis of recognition of interferon-alpha receptor by tyrosine kinase 2, Nat Struct Mol Biol, vol.21, issue.5, pp.443-451, 2014.

R. Ferrao and P. J. Lupardus, The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions, Front Endocrinol (Lausanne), vol.8, p.71, 2017.

R. D. Ferrao, H. J. Wallweber, and P. J. Lupardus, Receptor-mediated dimerization of JAK2 FERM domains is required for JAK2 activation, Elife, vol.7, 2018.

H. Quach, M. Rotival, J. Pothlichet, Y. E. Loh, M. Dannemann et al., Genetic Adaptation and Neandertal Admixture Shaped the Immune System of Human Populations, Cell, vol.167, issue.3, pp.643-56, 2016.
URL : https://hal.archives-ouvertes.fr/pasteur-01385620

D. Duffy, V. Rouilly, V. Libri, M. Hasan, B. Beitz et al., Functional analysis via standardized wholeblood stimulation systems defines the boundaries of a healthy immune response to complex stimuli, Immunity, vol.40, issue.3, pp.436-50, 2014.
URL : https://hal.archives-ouvertes.fr/pasteur-01384537

B. Piasecka, D. Duffy, A. Urrutia, H. Quach, P. E. Posseme et al., Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges, Proc Natl Acad Sci U S A, vol.115, issue.3, pp.488-97, 2018.
URL : https://hal.archives-ouvertes.fr/pasteur-01721850

C. A. Odhams, C. Graham, D. S. Vyse, and T. J. , Profiling RNA-Seq at multiple resolutions markedly increases the number of causal eQTLs in autoimmune disease, PLoS Genet, vol.13, issue.10, p.1007071, 2017.

Y. I. Li, B. Van-de-geijn, R. A. Knowles, D. A. Petti, A. A. Golan et al., RNA splicing is a primary link between genetic variation and disease, Science, vol.352, issue.6285, pp.600-604, 2016.

K. S. Manning and T. A. Cooper, The roles of RNA processing in translating genotype to phenotype, Nat Rev Mol Cell Biol, vol.18, issue.2, pp.102-116, 2017.

E. Park, Z. Pan, Z. Zhang, L. Lin, and Y. Xing, The Expanding Landscape of Alternative Splicing Variation in Human Populations, Am J Hum Genet, vol.102, issue.1, pp.11-26, 2018.

K. B. Nielsen, S. Sorensen, L. Cartegni, T. J. Corydon, T. K. Doktor et al., Seemingly neutral polymorphic variants may confer immunity to splicing-inactivating mutations: a synonymous SNP in exon 5 of MCAD protects from deleterious mutations in a flanking exonic splicing enhancer, Am J Hum Genet, vol.80, issue.3, pp.416-448, 2007.

A. P. Gregory, C. A. Dendrou, K. E. Attfield, A. Haghikia, D. K. Xifara et al., TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis, Nature, vol.488, issue.7412, pp.508-519, 2012.

K. P. Ng, A. M. Hillmer, C. T. Chuah, W. C. Juan, T. K. Ko et al., A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer, Nat Med, vol.18, issue.4, pp.521-529, 2012.

F. Matesanz, V. Potenciano, M. Fedetz, P. Ramos-mozo, A. Mdel et al., A functional variant that affects exon-skipping and protein expression of SP140 as genetic mechanism predisposing to multiple sclerosis, Hum Mol Genet, vol.24, pp.5619-5646, 2015.

B. J. Schmiedel, D. Singh, A. Madrigal, A. G. Valdovino-gonzalez, B. M. White et al., Impact of Genetic Polymorphisms on Human Immune, Cell Gene Expression. Cell, vol.175, issue.6, pp.1701-1716, 2018.

M. Rotival, H. Quach, and L. Quintana-murci, Defining the genetic and evolutionary architecture of alternative splicing in response to infection, Nat Commun, vol.10, issue.1, p.30975994, 2019.

J. K. Pickrell, A. A. Pai, Y. Gilad, and J. K. Pritchard, Noisy splicing drives mRNA isoform diversity in human cells, PLoS Genet, vol.6, issue.12, p.1001236, 2010.

F. A. Zouein, R. J. Duhe, and G. W. Booz, JAKs go nuclear: emerging role of nuclear JAK1 and JAK2 in gene expression and cell growth, Growth Factors, vol.29, issue.6, pp.245-52, 2011.

R. Potla, T. Koeck, J. Wegrzyn, S. Cherukuri, K. Shimoda et al., Tyk2 tyrosine kinase expression is required for the maintenance of mitochondrial respiration in primary pro-B lymphocytes, Mol Cell Biol, vol.26, issue.22, pp.8562-71, 2006.

M. Derecka, A. Gornicka, S. B. Koralov, K. Szczepanek, M. Morgan et al., Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity, Cell Metab, vol.16, issue.6, pp.814-838, 2012.

P. M. Van-koetsveld, G. Vitale, R. A. Feelders, M. Waaijers, D. M. Sprij-mooij et al., Interferonbeta is a potent inhibitor of cell growth and cortisol production in vitro and sensitizes human adrenocortical carcinoma cells to mitotane, Endocr Relat Cancer, vol.20, issue.3, pp.443-54, 2013.

L. Quatrini, E. Wieduwild, B. Escaliere, J. Filtjens, L. Chasson et al., Endogenous glucocorticoids control host resistance to viral infection through the tissue-specific regulation of PD-1 expression on NK cells, Nat Immunol, vol.19, issue.9, pp.954-62, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02086848

L. M. Franco, M. Gadkari, K. N. Howe, J. Sun, L. Kardava et al., Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses, J Exp Med, vol.216, issue.2, pp.384-406, 2019.

E. O. Glocker, D. Kotlarz, K. Boztug, E. M. Gertz, A. A. Schaffer et al., Inflammatory bowel disease and mutations affecting the interleukin-10 receptor, N Engl J Med, vol.361, issue.21, pp.2033-2078, 2009.

F. Charbit-henrion, B. Begue, A. Sierra, S. Hanein, M. C. Stolzenberg et al., Copy number variations and founder effect underlying complete IL-10Rbeta deficiency in Portuguese kindreds, PLoS One, vol.13, issue.10, p.205826, 2018.

M. G. Tovey, C. Lallemand, T. Safety, . Immunogenicity, and . Interferons, Pharmaceuticals (Basel), vol.3, issue.4, pp.1162-86, 2010.

K. Izumi, K. Mine, Y. Inoue, M. Teshima, S. Ogawa et al., Reduced Tyk2 gene expression in betacells due to natural mutation determines susceptibility to virus-induced diabetes, Nat Commun, vol.6, p.6748, 2015.

D. Diogo, L. Bastarache, K. P. Liao, R. R. Graham, R. S. Fulton et al., TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits, PLoS One, vol.10, issue.4, 2015.

E. Lopez-isac, D. Campillo-davo, L. Bossini-castillo, S. G. Guerra, S. Assassi et al., Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway, Epub 2015/09/05, 2015.

H. J. Westra, M. Martinez-bonet, S. Onengut-gumuscu, A. Lee, Y. Luo et al., Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes, Nat Genet, vol.50, issue.10, p.30224649, 2018.

S. E. Castel, A. Cervera, P. Mohammadi, F. Aguet, F. Reverter et al., Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk, Nat Genet, vol.50, issue.9, p.30127527, 2018.

P. Li, Y. K. Chang, K. W. Shek, and Y. L. Lau, Lack of association of TYK2 gene polymorphisms in Chinese patients with systemic lupus erythematosus, J Rheumatol, vol.38, issue.1, pp.177-185, 2011.

L. Tang, P. Wan, Y. Wang, J. Pan, Y. Wang et al., Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population, Inflamm Res, vol.64, issue.10, pp.817-841, 2015.

K. Sato, M. Shiota, S. Fukuda, E. Iwamoto, H. Machida et al., Strong evidence of a combination polymorphism of the tyrosine kinase 2 gene and the signal transducer and activator of transcription 3 gene as a DNA-based biomarker for susceptibility to Crohn's disease in the japanese population, J Clin Immunol, 2009.

C. Kyogoku, A. Morinobu, K. Nishimura, D. Sugiyama, H. Hashimoto et al., Lack of association between tyrosine kinase 2 (TYK2) gene polymorphisms and susceptibility to SLE in a Japanese population, Mod Rheumatol, vol.19, issue.4, pp.401-407, 2009.

S. Nagafuchi, Y. Kamada-hibio, K. Hirakawa, N. Tsutsu, M. Minami et al., TYK2 Promoter Variant and Diabetes Mellitus in the Japanese, EBioMedicine, vol.2, issue.7, pp.744-753, 2015.

P. Eid and M. G. Tovey, Characterization of a domain of a human type I interferon receptor protein involved in ligand binding, J Interferon Cytokine Res, vol.15, issue.3, pp.205-216, 1995.

F. A. Ran, P. D. Hsu, J. Wright, V. Agarwala, D. A. Scott et al., Genome engineering using the CRISPR-Cas9 system, Nat Protoc, vol.8, issue.11, pp.2281-308, 2013.

C. Trapnell, B. A. Williams, G. Pertea, A. Mortazavi, G. Kwan et al., Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation, Nat Biotechnol, vol.28, issue.5, pp.511-516, 2010.

S. Anders, A. Reyes, and W. Huber, Detecting differential usage of exons from RNA-seq data, Genome Res, vol.22, issue.10, pp.2008-2025, 2012.

S. Anders, P. T. Pyl, and W. Huber, HTSeq-a Python framework to work with high-throughput sequencing data, Bioinformatics, vol.31, issue.2, pp.166-175, 2015.

Y. I. Li, D. A. Knowles, J. Humphrey, A. N. Barbeira, S. P. Dickinson et al., Annotation-free quantification of RNA splicing using LeafCutter, Nat Genet, vol.50, issue.1, p.29229983, 2018.

A. A. Shabalin, Matrix eQTL: ultra fast eQTL analysis via large matrix operations, Bioinformatics, vol.28, issue.10, pp.1353-1361, 2012.

S. Thomas, V. Rouilly, P. E. Alanio, C. Dubois, A. Delval et al., The Milieu Interieur study-an integrative approach for study of human immunological variance, Clin Immunol, vol.157, issue.2, pp.277-93, 2015.
URL : https://hal.archives-ouvertes.fr/pasteur-01291879

A. O. Thomas, D. J. Jackson, M. D. Evans, V. Rajamanickam, R. E. Gangnon et al., Sex-related differences in pulmonary physiologic outcome measures in a high-risk birth cohort, J Allergy Clin Immunol, vol.136, issue.2, pp.282-289, 2015.

Y. S. Aulchenko, S. Ripke, A. Isaacs, and C. M. Van-duijn, GenABEL: an R library for genome-wide association analysis, Bioinformatics, vol.23, issue.10, pp.1294-1300, 2007.