Genetics of Human Immunity Lab News and Publications

Brooks, D. R., Koh, H. Y., Kerrins, T. M., Lang, S., Bland, E., Yang, R., Nicholas, S. K., Sikkink, S. J., Kralik, S., Eng, C., Murali, C. N., Lalani, S., Magoulas, P. L., Emrick, L., Fisher, K. S., & Scaglia, F. (2026). JAK inhibition in PNPT1-related mitochondrial interferonopathy: A case report and review of mitochondrial-immune crosstalk. JIMD Reports, 67(4), e70096. https://doi.org/10.1002/jmd2.70096

Yang, R., & Chinn, I. K. (2026). Key and emerging concepts in inborn errors of immunity and immune dysregulation. Journal of Allergy and Clinical Immunology, 158(1), 12–25.e1. https://doi.org/10.1016/j.jaci.2026.05.001

Yang, R., Turunbedu, S. K., Nandiwada, S., Curry, C. V., Elghetany, T. M., Scull, B., Geng, J., Vargas-Hernandez, A., Chinn, I. K., Ochoa, S., Allen, C. E., & Satter, L. F. (2026). Distinct EBV-associated phenotypes due to a novel homozygous missense variant in CD27. bioRxiv. https://doi.org/10.64898/2026.01.15.698722

Ogishi, M., Puchan, J., Yang, R., Arias, A. A., Han, J. E., Nguyen, T., Gutiérrez-Cózar, R., Conil, C., Seeleuthner, Y., Rinchai, D., Zhang, P., Ponsin, K., Chaldebas, M., Feng, Y., Neehus, A. L., Delmonte, O. M., Khan, T., Landegren, N., Eriksson, D., … Casanova, J.-L. (2025). Human LY9 governs CD4+ T cell IFN-γ immunity to Mycobacterium tuberculosis. Science Immunology, 10(107), eads7377. https://doi.org/10.1126/sciimmunol.ads7377

Ogishi, M., Kitaoka, K., Good-Jacobson, K. L., Rinchai, D., Zhang, B., Wang, J., Gies, V., Rao, G., Nguyen, T., Avery, D. T., Khan, T., Smithmyer, M. E., Mackie, J., Yang, R., Arias, A. A., Asano, T., Ponsin, K., Chaldebas, M., Zhang, P., … Tangye, S. G. (2024). Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling. Immunity, 57(12), 2790–2807.e15. https://doi.org/10.1016/j.immuni.2024.10.014

Arias, A. A., Neehus, A. L., Ogishi, M., Meynier, V., Krebs, A., Lazarov, T., Lee, A. M., Arango-Franco, C. A., Yang, R., Orrego, J., Corcini Berndt, M., Rojas, J., Li, H., Rinchai, D., Erazo-Borrás, L., Han, J. E., Pillay, B., Ponsin, K., Chaldebas, M., … Boisson-Dupuis, S. (2024). Tuberculosis in otherwise healthy adults with inherited TNF deficiency. Nature, 633(8029), 417–425. https://doi.org/10.1038/s41586-024-07866-3

Peel, J. N., Yang, R., Le Voyer, T., Gervais, A., Rosain, J., Bastard, P., Behere, A., Cederholm, A., Bodansky, A., Seeleuthner, Y., Conil, C., Ding, J. Y., Lei, W. T., Bizien, L., Soudée, C., Migaud, M., Ogishi, M., Yatim, A., Lee, D., … Casanova, J.-L. (2024). Neutralizing IFN-γ autoantibodies are rare and pathogenic in HLA-DRB1*15:02 or 16:02 individuals. Journal of Clinical Investigation, 134(8), e178263. https://doi.org/10.1172/JCI178263

Bohlen, J., Zhou, Q., Philippot, Q., Ogishi, M., Rinchai, D., Nieminen, T., Seyedpour, S., Parvaneh, N., Rezaei, N., Yazdanpanah, N., Momenilandi, M., Conil, C., Neehus, A. L., Schmidt, C., Arango-Franco, C. A., Le Voyer, T., Khan, T., Yang, R., Puchan, J., … Casanova, J.-L. (2023). Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria. Cell, 186(23), 5114–5134.e27. https://doi.org/10.1016/j.cell.2023.09.024

Zhang, P., Abel, L., Casanova, J.-L., & Yang, R. (2023). Genotyping multiplexed-sequencing of CRISPR-localized editing (GMUSCLE): An experimental and computational approach for analyzing CRISPR-edited cells. The CRISPR Journal, 6(5), 462–472. https://doi.org/10.1089/crispr.2023.0021

Ogishi, M., Yang, R., Rosain, J., Bustamante, J., Casanova, J.-L., & Boisson-Dupuis, S. (2023). Inborn errors of human transcription factors governing IFN-γ antimycobacterial immunity. Current Opinion in Immunology, 81, 102296. https://doi.org/10.1016/j.coi.2023.102296

Philippot, Q., Ogishi, M., Bohlen, J., Puchan, J., Arias, A. A., Nguyen, T., Martin-Fernandez, M., Conil, C., Rinchai, D., Momenilandi, M., Mahdaviani, S. A., Keramatipour, M., Rosain, J., Yang, R., Khan, T., Neehus, A. L., Materna, M., Han, J. E., Peel, J., … Puel, A. (2023). Human IL-23 is essential for IFN-γ-dependent immunity to mycobacteria. Science Immunology, 8(80), eabq5204. https://doi.org/10.1126/sciimmunol.abq5204

Rosain, J., Neehus, A. L., Manry, J., Yang, R., Le Pen, J., Daher, W., Liu, Z., Chan, Y. H., Tahuil, N., Türel, Ö., Bourgey, M., Ogishi, M., Doisne, J.-M., Izquierdo, H. M., Shirasaki, T., Le Voyer, T., Guérin, A., Bastard, P., Moncada-Vélez, M., … Bustamante, J. (2023). Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria. Cell, 186(3), 621–645.e33. https://doi.org/10.1016/j.cell.2022.12.038

Ogishi, M., Yang, R., Rodriguez, R., Golec, D. P., Martin, E., Philippot, Q., Bohlen, J., Pelham, S. J., Arias, A. A., Khan, T., Ata, M., Al Ali, F., Rozenberg, F., Kong, X. F., Chrabieh, M., Laine, C., Lei, W. T., Han, J. E., Seeleuthner, Y., … Boisson-Dupuis, S. (2023). Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis. Journal of Experimental Medicine, 220(1), e20220484. https://doi.org/10.1084/jem.20220484

Ogishi, M., Arias, A. A., Yang, R., Han, J. E., Zhang, P., Rinchai, D., Halpern, J., Mulwa, J., Keating, N., Chrabieh, M., Lainé, C., Seeleuthner, Y., Ramírez-Alejo, N., Nekooie-Marnany, N., Guennoun, A., Muller-Fleckenstein, I., Fleckenstein, B., Kilic, S. S., Minegishi, Y., … Boisson-Dupuis, S. (2022). Impaired IL-23-dependent induction of IFN-γ underlies mycobacterial disease in patients with inherited TYK2 deficiency. Journal of Experimental Medicine, 219(10), e20220094. https://doi.org/10.1084/jem.20220094

Croft, C. A., Thaller, A., Marie, S., Doisne, J.-M., Surace, L., Yang, R., Puel, A., Bustamante, J., Casanova, J.-L., & Di Santo, J. P. (2022). Notch, RORC and IL-23 signals cooperate to promote multi-lineage human innate lymphoid cell differentiation. Nature Communications, 13, 4344. https://doi.org/10.1038/s41467-022-32089-3

Yang, R., Avery, D. T., Jackson, K. J. L., Ogishi, M., Benhsaien, I., Du, L., Ye, X., Han, J., Rosain, J., Peel, J. N., Alyanakian, M. A., Neven, B., Winter, S., Puel, A., Boisson, B., Payne, K. J., Wong, M., Russell, A. J., Mizoguchi, Y., … Tangye, S. G. (2022). Human T-bet governs the generation of a distinct subset of CD11c-high CD21-low B cells. Science Immunology, 7(73), eabq3277. https://doi.org/10.1126/sciimmunol.abq3277

Spaan, A. N., Neehus, A. L., Laplantine, E., Staels, F., Ogishi, M., Seeleuthner, Y., Rapaport, F., Lacey, K. A., Van Nieuwenhove, E., Chrabieh, M., Hum, D., Migaud, M., Izmiryan, A., Lorenzo, L., Kochetkov, T., Heesterbeek, D. A. C., Bardoel, B. W., DuMont, A. L., Dobbs, K., … Casanova, J.-L. (2022). Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin. Science, 376(6599), eabm6380. https://doi.org/10.1126/science.abm6380

Manry, J., Bastard, P., Gervais, A., Le Voyer, T., Rosain, J., Philippot, Q., Michailidis, E., Hoffmann, H.-H., Eto, S., Garcia-Prat, M., Bizien, L., Parra-Martínez, A., Yang, R., Haljasmägi, L., Migaud, M., Särekannu, K., Maslovskaja, J., de Prost, N., Tandjaoui-Lambiotte, Y., … Gervais, A. (2022). The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies. Proceedings of the National Academy of Sciences of the United States of America, 119(21), e2200413119. https://doi.org/10.1073/pnas.2200413119

Benhsaien, I., Yang, R., Ailal, F., Weisshaar, M., Mele, F., Casanova, J.-L., Bustamante, J., & Bousfiha, A. (2022). Chronic upper airway inflammation related to high Th2 cytokines in a case of Mendelian susceptibility to mycobacterial disease. Qatar Medical Journal, 2022(2), 24. https://doi.org/10.5339/qmj.2022.fqac.24

Zhang, Q., Bastard, P., COVID Human Genetic Effort, Cobat, A., & Casanova, J.-L. (2022). Human genetic and immunological determinants of critical COVID-19 pneumonia. Nature, 603(7902), 587–598. https://doi.org/10.1038/s41586-022-04447-0

Valença-Pereira, F., Fang, Q., Marié, I. J., Giddings, E. L., Fortner, K. A., Yang, R., Villarino, A. V., Huang, Y. H., Frank, D. A., Wen, H., Levy, D. E., & Rincon, M. (2021). IL-6 enhances CD4 cell motility by sustaining mitochondrial Ca2+ through the noncanonical STAT3 pathway. Proceedings of the National Academy of Sciences of the United States of America, 118(37), e2103444118. https://doi.org/10.1073/pnas.2103444118

Lévy, R., Langlais, D., Béziat, V., Rapaport, F., Rao, G., Lazarov, T., Bourgey, M., Zhou, Y. J., Briand, C., Moriya, K., Ailal, F., Avery, D. T., Markle, J., Lim, A. I., Ogishi, M., Yang, R., Pelham, S., Emam, M., Migaud, M., … Puel, A. (2021). Inherited human c-Rel deficiency disrupts myeloid and lymphoid immunity to multiple infectious agents. Journal of Clinical Investigation, 131(17), e150143. https://doi.org/10.1172/JCI150143

Bastard, P., Gervais, A., Le Voyer, T., Rosain, J., Philippot, Q., Manry, J., Michailidis, E., Hoffmann, H.-H., Eto, S., Garcia-Prat, M., Bizien, L., Parra-Martínez, A., Yang, R., Haljasmägi, L., Migaud, M., Särekannu, K., Maslovskaja, J., de Prost, N., Tandjaoui-Lambiotte, Y., … Casanova, J.-L. (2021). Autoantibodies neutralizing type I IFNs are present in approximately 4% of uninfected individuals over 70 years old and account for approximately 20% of COVID-19 deaths. Science Immunology, 6(62), eabl4340. https://doi.org/10.1126/sciimmunol.abl4340

Béziat, V., Rapaport, F., Hu, J., Titeux, M., Bonnet des Claustres, M., Bourgey, M., Griffin, H., Bandet, É., Ma, C. S., Sherkat, R., Rokni-Zadeh, H., Louis, D. M., Changi-Ashtiani, M., Delmonte, O. M., Fukushima, T., Habib, T., Guennoun, A., Khan, T., Bender, N., … Casanova, J.-L. (2021). Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy. Cell, 184(14), 3812–3828.e30. https://doi.org/10.1016/j.cell.2021.06.004

Ogishi, M., Yang, R., Aytekin, C., Langlais, D., Bourgey, M., Khan, T., Al Ali, F., Rahman, M., Delmonte, O. M., Chrabieh, M., Zhang, P., Gruber, C., Pelham, S. J., Spaan, A. N., Rosain, J., Lei, W. T., Drutman, S., Hellmann, M. D., Callahan, M. K., … Casanova, J.-L. (2021). Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child. Nature Medicine, 27(9), 1646–1654. https://doi.org/10.1038/s41591-021-01388-5

Yang, R., Weisshaar, M., Mele, F., Benhsaien, I., Dorgham, K., Han, J., Croft, C. A., Notarbartolo, S., Rosain, J., Bastard, P., Puel, A., Fleckenstein, B., Glimcher, L. H., Di Santo, J. P., Ma, C. S., Gorochov, G., Bousfiha, A., Abel, L., Tangye, S. G., … Sallusto, F. (2021). High Th2 cytokine levels and upper airway inflammation in human inherited T-bet deficiency. Journal of Experimental Medicine, 218(8), e20202726. https://doi.org/10.1084/jem.20202726

Le Voyer, T., Neehus, A. L., Yang, R., Ogishi, M., Rosain, J., Alroqi, F., Alshalan, M., Blumental, S., Al Ali, F., Khan, T., Ata, M., Rozen, L., Demulder, A., Bastard, P., Gruber, C., Roynard, M., Seeleuthner, Y., Rapaport, F., Bigio, B., … Bustamante, J. (2021). Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease. Proceedings of the National Academy of Sciences of the United States of America, 118(15), e2102804118. https://doi.org/10.1073/pnas.2102804118

Bastard, P., Michailidis, E., Hoffmann, H.-H., Chbihi, M., Le Voyer, T., Rosain, J., Philippot, Q., Seeleuthner, Y., Gervais, A., Materna, M., de Oliveira, P. M. N., Maia, M. L. S., Dinis Ano Bom, A. P., Azamor, T., Araújo da Conceição, D., Goudouris, E., Homma, A., Slesak, G., Schäfer, J., … Casanova, J.-L. (2021). Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. Journal of Experimental Medicine, 218(4), e20202486. https://doi.org/10.1084/jem.20202486

Ogishi, M., Yang, R., Gruber, C., Zhang, P., Pelham, S. J., Spaan, A. N., Rosain, J., Chbihi, M., Han, J. E., Rao, V. K., Kainulainen, L., Bustamante, J., Boisson, B., Bogunovic, D., Boisson-Dupuis, S., & Casanova, J.-L. (2021). Multibatch cytometry data integration for optimal immunophenotyping. Journal of Immunology, 206(1), 206–213. https://doi.org/10.4049/jimmunol.2000854

Zhang, Q., Bastard, P., Bolze, A., Jouanguy, E., Zhang, S.-Y., COVID Human Genetic Effort, Cobat, A., Notarangelo, L. D., Su, H. C., Abel, L., & Casanova, J.-L. (2020). Life-threatening COVID-19: Defective interferons unleash excessive inflammation. Med, 1(1), 14–20. https://doi.org/10.1016/j.medj.2020.12.001

Yang, R., Mele, F., Worley, L., Langlais, D., Rosain, J., Benhsaien, I., Elarabi, H., Croft, C. A., Doisne, J.-M., Zhang, P., Weisshaar, M., Jarrossay, D., Latorre, D., Shen, Y., Han, J., Ogishi, M., Gruber, C., Markle, J., Al Ali, F., … Casanova, J.-L. (2020). Human T-bet governs innate and innate-like adaptive IFN-γ immunity against mycobacteria. Cell, 183(7), 1826–1847.e31. https://doi.org/10.1016/j.cell.2020.10.046

Zhang, Q., Bastard, P., Liu, Z., Le Pen, J., Moncada-Velez, M., Chen, J., Ogishi, M., Sabli, I. K. D., Hodeib, S., Korol, C., Rosain, J., Bilguvar, K., Ye, J., Bolze, A., Bigio, B., Yang, R., Arias, A. A., Zhou, Q., Zhang, Y., … Casanova, J.-L. (2020). Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science, 370(6515), eabd4570. https://doi.org/10.1126/science.abd4570

Bastard, P., Rosen, L. B., Zhang, Q., Michailidis, E., Hoffmann, H.-H., Zhang, Y., Dorgham, K., Philippot, Q., Rosain, J., Béziat, V., Manry, J., Shaw, E., Haljasmägi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A. A., … Casanova, J.-L. (2020). Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science, 370(6515), eabd4585. https://doi.org/10.1126/science.abd4585

Kerner, G., Rosain, J., Guérin, A., Al-Khabaz, A., Oleaga-Quintas, C., Rapaport, F., Massaad, M. J., Ding, J. Y., Khan, T., Al Ali, F., Rahman, M., Deswarte, C., Martinez-Barricarte, R., Geha, R. S., Jeanne-Julien, V., Garcia, D., Chi, C.-Y., Yang, R., Roynard, M., … Bustamante, J. (2020). Inherited human IFN-γ deficiency underlies mycobacterial disease. Journal of Clinical Investigation, 130(6), 3158–3171. https://doi.org/10.1172/JCI135460

Kerner, G., Ramirez-Alejo, N., Seeleuthner, Y., Yang, R., Ogishi, M., Cobat, A., Patin, E., Quintana-Murci, L., Boisson-Dupuis, S., Casanova, J.-L., & Abel, L. (2019). Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry. Proceedings of the National Academy of Sciences of the United States of America, 116(21), 10430–10434. https://doi.org/10.1073/pnas.1903561116

Yang, R., Masters, A. R., Fortner, K. A., Champagne, D. P., Yanguas-Casás, N., Silberger, D. J., Weaver, C. T., Haynes, L., & Rincon, M. (2016). IL-6 promotes the differentiation of a subset of naive CD8+ T cells into IL-21-producing B helper CD8+ T cells. Journal of Experimental Medicine, 213(11), 2281–2291. https://doi.org/10.1084/jem.20160417

Champagne, D. P., Hatle, K. M., Fortner, K. A., D’Alessandro, A., Thornton, T. M., Yang, R., Torralba, D., Tomás-Cortázar, J., Jun, Y. W., Ahn, K. H., Hansen, K. C., Haynes, L., Anguita, J., & Rincon, M. (2016). Fine-tuning of CD8+ T cell mitochondrial metabolism by the respiratory chain repressor MCJ dictates protection to influenza virus. Immunity, 44(6), 1299–1311. https://doi.org/10.1016/j.immuni.2016.02.018

Yang, R., & Rincon, M. (2016). Mitochondrial Stat3, the need for design thinking. International Journal of Biological Sciences, 12(5), 532–544. https://doi.org/10.7150/ijbs.15153

Dong, W., Yang, R., Yang, J., Yang, J., Ding, J., Wu, H., & Zhang, J. (2015). Resveratrol pretreatment protects rat hearts from ischemia/reperfusion injury partly via a NALP3 inflammasome pathway. International Journal of Clinical and Experimental Pathology, 8(8), 8731–8741.

Yang, J., Guo, X., Yang, J., Ding, J. W., Li, S., Yang, R., Fan, Z. X., & Yang, C. J. (2015). RP105 protects against apoptosis in ischemia/reperfusion-induced myocardial damage in rats by suppressing TLR4-mediated signaling pathways. Cellular Physiology and Biochemistry, 36(6), 2137–2148. https://doi.org/10.1159/000430180

Yang, R., Lirussi, D., Thornton, T. M., Jelley-Gibbs, D. M., Diehl, S. A., Case, L. K., Madesh, M., Taatjes, D. J., Teuscher, C., Haynes, L., & Rincón, M. (2015). Mitochondrial Ca2+ and membrane potential, an alternative pathway for interleukin 6 to regulate CD4 cell effector function. eLife, 4, e06376. https://doi.org/10.7554/eLife.06376

Yang, J., Zhang, X. D., Yang, J., Ding, J. W., Liu, Z. Q., Li, S. G., & Yang, R. (2011). The cardioprotective effect of fluvastatin on ischemic injury via down-regulation of toll-like receptor 4. Molecular Biology Reports, 38(5), 3037–3044. https://doi.org/10.1007/s11033-010-9970-z