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1. Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2

Author

Walsh, Jaclyn M. L., Miao, Vincent N., Owings, Anna H., Tang, Ying, Bromley, Joshua D., Kazer, Samuel W., Kimler, Kyle, Asare, Chelsea, Ziegler, Carly G. K., Ibrahim, Samira, Jivanjee, Tasneem, George, Micayla, Navia, Andrew W., Drake, Riley S., Parker, Adam, Billingsley, Benjamin C., Dotherow, Paul, Tarugu, Spurthi, Kota, Sai K., Laird, Hannah, Wichman, T. Grant, Davis, Yesenia T., Dhaliwal, Neha S., Pride, Yilianys, Guo, Yanglin, Senitko, Michal, Harvey, Jessie, Bates, John T., Diamond, Gill, Garrett, Michael R., Robinson, D. Ashley, Frame, I. J., Lyons, Jonathan J., Robinson, Tanya O., Shalek, Alex K., Horwitz, Bruce H., Glover, Sarah C., and Ordovas-Montanes, Jose

Published
2025
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3. Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.

Author

Omdahl, Kayleigh Ingersoll, Bermea, Rene S., Fleming, Ryan, Kimler, Kyle, Kaminski, James, Hariri, Lida P., Ly, Amy, Rui, Xianliang, Cagnin, Lorenzo, Lane, Jennifer, Gerdemann, Ulrike, Blazar, Bruce R., Tkachev, Victor, and Kean, Leslie S.

Subjects
HEMATOPOIETIC stem cell transplantation, T cell receptors, CELLULAR evolution, T cells, HEMATOPOIETIC stem cells
Abstract

Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing. Transcriptional profiling revealed substantial biological differences between T cells infiltrating the lung and liver during aGVHD. These included enrichment for transcriptional pathways controlling extracellular matrix remodeling and chemotaxis in the lung and enrichment for transcriptional pathways linked to nucleic acid metabolism and proliferation in the liver. Single-cell RNA sequencing and TCR sequencing substantiated divergent organ-specific transcriptional programing of tissue-infiltrating T cells, which was linked to clonal expansion, with expanded clones progressively enriched for C-X3-C motif chemokine receptor 1 (CX3CR1)–expressing CD8 effector T cells in the lung and eomesodermin (EOMES)–expressing CD8 effector-memory T cells in the liver. This divergent evolution of T cells was maintained even for T cells sharing the same TCRs, indicating its independence from antigen specificity. Together, these results provide insights into the role that tissue microenvironment–derived signals play in local T cell transcriptional programming during alloimmune-mediated clonal expansion and suggest potential opportunities to develop tissue-specific therapeutics to curtail pathogenic immunity after transplant. Editor's summary: Acute graft-versus-host disease (aGVHD) driven by T cells after allogeneic hematopoietic stem cell transplant (HCT) can occur in several different organs and tissues. Here, Omdahl et al. sought to understand how post-HCT T cell responses are shaped in two commonly affected organs, the lungs and the liver, using a cohort of nonhuman primates that underwent allogeneic HCT. The authors found that T cells from the different tissues acquired distinct transcriptional programs and phenotypes. This was true even for T cells carrying the same T cell receptor, hinting that the environment was the driver of the divergent phenotypes. These data suggest that T cell–targeting treatments for aGVHD could be tailored on the basis of the affected organs. —Courtney Malo [ABSTRACT FROM AUTHOR]

Published
2025
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4. Reshaping of Local Alloimmunity By Organ-Specific Microenvironments during Acute Gvhd.

Author

Omdahl, Kayleigh Ingersoll, primary, Bermea, Rene S., additional, Fleming, Ryan, additional, Kimler, Kyle, additional, Hariri, Lida P., additional, Ly, Amy, additional, Rui, Xianliang, additional, Lane, Jennifer, additional, Kaminski, James, additional, Gerdemann, Ulrike, additional, Blazar, Bruce R., additional, Kean, Leslie S., additional, and Tkachev, Victor, additional

Published
2024
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5. Concerted changes in the pediatric single-cell intestinal ecosystem before and after anti-TNF blockade

Author

Zheng, Hengqi Betty, primary, Doran, Benjamin A., additional, Kimler, Kyle, additional, Yu, Alison, additional, Tkachev, Victor, additional, Niederlova, Veronika, additional, Cribbin, Kayla, additional, Fleming, Ryan, additional, Bratrude, Brandi, additional, Betz, Kayla, additional, Cagnin, Lorenzo, additional, McGuckin, Connor, additional, Keskula, Paula, additional, Albanese, Alexandre, additional, Sacta, Maria, additional, de Sousa Casal, Joshua, additional, van Esch, Ruben, additional, Kwong, Andrew C., additional, Kummerlowe, Conner, additional, Taliaferro, Faith, additional, Fiaschi, Nathalie, additional, Kou, Baijun, additional, Coetzee, Sandra, additional, Jalal, Sumreen, additional, Yabe, Yoko, additional, Dobosz, Michael, additional, Wipperman, Matthew F., additional, Hamon, Sara, additional, Kalliolias, George D., additional, Hooper, Andrea, additional, Lim, Wei Keat, additional, Haxhinasto, Sokol, additional, Wei, Yi, additional, Ford, Madeline, additional, Ambartsumyan, Lusine, additional, Suskind, David L., additional, Lee, Dale, additional, Deutsch, Gail, additional, Deng, Xuemei, additional, Collen, Lauren V., additional, Mitsialis, Vanessa, additional, Snapper, Scott B., additional, Wahbeh, Ghassan, additional, Shalek, Alex K., additional, Ordovas-Montanes, Jose, additional, and Kean, Leslie S., additional

Published
2023
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6. Single-Cell RNA-Seq Reveals an Interferon-Driven Inflammatory CD4 Naïve T Cell Subpopulation at Day 100 in Hematopoietic Stem Cell Transplant Patients That Ultimately Develop Chronic Gvhd

Author

Albanese, Alexandre, primary, Chen, Edward, additional, Zavistaski, Jillian, additional, Betz, Kayla, additional, Suessmuth, Yvonne, additional, Cagnin, Lorenzo S, additional, Keskula, Paula, additional, Kimler, Kyle, additional, Kaminski, James, additional, Blazar, Bruce R., additional, Watkins, Benjamin K., additional, and Kean, Leslie S., additional

Published
2023
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8. Single-Cell RNA-Seq Reveals an Interferon-Driven Inflammatory CD4 Naïve T Cell Subpopulation at Day 100 in Hematopoietic Stem Cell Transplant Patients That Ultimately Develop Chronic Gvhd

Author

Albanese, Alexandre, primary, Chen, Edward, additional, Zavistaski, Jillian, additional, Betz, Kayla, additional, Suessmuth, Yvonne, additional, Cagnin, Lorenzo, additional, Keskula, Paula, additional, Kimler, Kyle, additional, Kaminski, James, additional, Blazar, Bruce R., additional, Watkins, Benjamin, additional, and Kean, Leslie S., additional

Published
2022
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11. Concerted changes in the pediatric single-cell intestinal ecosystem before and after anti-TNF blockade

Author

Zheng, Hengqi Betty, primary, Doran, Benjamin A., additional, Kimler, Kyle, additional, Yu, Alison, additional, Tkachev, Victor, additional, Niederlova, Veronika, additional, Cribbin, Kayla, additional, Fleming, Ryan, additional, Bratrude, Brandi, additional, Betz, Kayla, additional, Cagnin, Lorenzo, additional, McGuckin, Connor, additional, Keskula, Paula, additional, Albanese, Alexandre, additional, Sacta, Maria, additional, de Sousa Casal, Joshua, additional, van Esch, Ruben, additional, Kwong, Andrew C., additional, Kummerlowe, Conner, additional, Taliaferro, Faith, additional, Fiaschi, Nathalie, additional, Kou, Baijun, additional, Coetzee, Sandra, additional, Jalal, Sumreen, additional, Yabe, Yoko, additional, Dobosz, Michael, additional, Wipperman, Matthew F., additional, Hamon, Sara, additional, Kalliolias, George D., additional, Hooper, Andrea, additional, Lim, Wei Keat, additional, Haxhinasto, Sokol, additional, Wei, Yi, additional, Ford, Madeline, additional, Ambartsumyan, Lusine, additional, Suskind, David L., additional, Lee, Dale, additional, Deutsch, Gail, additional, Deng, Xuemei, additional, Collen, Lauren V., additional, Mitsialis, Vanessa, additional, Snapper, Scott B., additional, Wahbeh, Ghassan, additional, Shalek, Alex K., additional, Ordovas-Montanes, Jose, additional, and Kean, Leslie S., additional

Published
2021
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13. Protein allocation and utilization in the versatile chemolithoautotroph Cupriavidus necator

Author

Jahn, Michael, Crang, Nick, Janasch, Markus, Hober, Andreas, Forsström, Björn, Kimler, Kyle, Mattausch, Alexander, Chen, Qi, Asplund-Samuelsson, Johannes, Hudson, Elton P., Jahn, Michael, Crang, Nick, Janasch, Markus, Hober, Andreas, Forsström, Björn, Kimler, Kyle, Mattausch, Alexander, Chen, Qi, Asplund-Samuelsson, Johannes, and Hudson, Elton P.

Abstract

Bacteria must balance the different needs for substrate assimilation, growth functions, and resilience in order to thrive in their environment. Of all cellular macromolecules, the bacterial proteome is by far the most important resource and its size is limited. Here, we investigated how the highly versatile 'knallgas' bacterium Cupriavidus necator reallocates protein resources when grown on different limiting substrates and with different growth rates. We determined protein quantity by mass spectrometry and estimated enzyme utilization by resource balance analysis modeling. We found that C. necator invests a large fraction of its proteome in functions that are hardly utilized. Of the enzymes that are utilized, many are present in excess abundance. One prominent example is the strong expression of CBB cycle genes such as Rubisco during growth on fructose. Modeling and mutant competition experiments suggest that CO2-reassimilation through Rubisco does not provide a fitness benefit for heterotrophic growth, but is rather an investment in readiness for autotrophy., See also peer review documents at DOI 10.7554/eLife.69019.sa0 10.7554/eLife.69019.sa1 10.7554/eLife.69019.sa2QC 20220111

Published
2021
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