Research

The Henrickson Lab investigates the role of T cell dysfunction in chronic inflammatory disease and primary immunodeficiency.

The impact on T cell immunometabolic function in chronic inflammation is a key focus of the Henrickson lab.  We are studying the impact of pediatric asthma and obesity on immune function, including the response to vaccines.  The hypotheses from initial human studies are being tested in mouse models of obese asthma and in human cell in vitro, and extended in new human studies. 
The Henrickson Lab investigates also focuses on mechanisms of T cell dysfunction in primary immunodeficiency.
The lab has studied the earliest stages of T cell activation and has used whole-exome sequencing to uncover novel causes of immunodeficiency in families with severe persistent skin viral infections with genetic disease. The lab is now starting a study T cell immunometabolic dysfunction in primary immunodeficiency.

To conduct its studies, the lab uses complementary approaches in humans and mice, leveraging detailed immunophenotyping and metabolic characterization of immune dysfunction in patients in order to identify mechanistic hypotheses to test in mouse models and human cells in vitro.

RECENT RESEARCH PAPERS

Briones AC, Megino RF, Marin AV, Chacón-Arguedas D, García-Martinez E, Balastegui-Martín H, Reyburn HT, Henrickson SE, Rodríguez-Sainz C, Seoane-Reula E, Sanchez-Mateos P, Cardenas PP, Regueiro JR. Nonsense CD247 mutations show dominant-negative features in T-cell receptor expression and function. J Allergy Clin Immunol. 2024 Oct;154(4):1022-1032. doi: 10.1016/j.jaci.2024.06.019. Epub 2024 Jul 9. PMID: 38992472.

Gong Q, Sharma M, Kuan EL, Glass MC, Chander A, Singh M, Graybuck LT, Thomson ZJ, LaFrance CM, Zaim SR, Peng T, Okada LY, Genge PC, Henderson KE, Dornisch EM, Layton ED, Wittig PJ, Heubeck AT, Mukuka NM, Reading J, Roll CR, Hernandez V, Parthasarathy V, Stuckey TJ, Musgrove B, Swanson E, Lord C, Weiss MDA, Phalen CG, Mettey RR, Lee KJ, Johanneson JB, Kawelo EK, Garber J, Krishnan U, Smithmyer M, Wherry EJ, Vella L, Henrickson SE, Kopp MS, Savage AK, Becker LA, Meijer P, Coffey EM, Goronzy JJ, Speake C, Bumol TF, Goldrath AW, Torgerson TR, Li XJ, Skene PJ, Buckner JH, Gustafson CE. Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults. bioRxiv [Preprint]. 2024 Sep 14:2024.09.10.612119. doi: 10.1101/2024.09.10.612119. PMID: 39314416; PMCID: PMC11419011.

Castaño D, Wang S, Atencio-Garcia S, Shields EJ, Rico MC, Sharpe H, Bustamante J, Feng A, Le Coz C, Romberg N, Tobias JW, Utz PJ, Henrickson SE, Casanova JL, Bonasio R, Locci M. IL-12 drives the differentiation of human T follicular regulatory cells. Sci Immunol. 2024 Jul 5;9(97):eadf2047. doi: 10.1126/sciimmunol.adf2047. Epub 2024 Jul 5. PMID: 38968337.

De Roos AJ, Senter JP, Schinasi LH, Huang W, Moore K, Maltenfort M, Forrest C, Henrickson SE, Kenyon CC. Outdoor aeroallergen impacts on asthma exacerbation among sensitized and nonsensitized Philadelphia children. J Allergy Clin Immunol Glob. 2024 Mar 25;3(3):100248. doi: 10.1016/j.jacig.2024.100248. PMID: 38645670; PMCID: PMC11024998.

Materna, M., Delmonte, O. M., Bosticardo, M., Momenilandi, M., Conrey, P. E., Charmeteau-De Muylder, B., Bravetti, C., Bellworthy, R., Cederholm, A., Staels, F., Ganoza, C. A., Darko, S., Sayed, S., Le Floc’h, C., Ogishi, M., Rinchai, D., Guenoun, A., Bolze, A., Khan, T., Gervais, A., … Béziat, V. (2024). The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants. Science (New York, N.Y.)383(6686), eadh4059. https://doi.org/10.1126/science.adh4059

Conrey PE*, Denu L*, O’Boyle KC*, Rozich I*, Green J, Maslanka J, Lubin JB, Duranova T, Haltzman BL, Gianchetti L, Oldridge DA, De Luna N, Vella LA, Allman D, Spergel JM, Tanes C, Bittinger K, Henrickson SE*, Silverman MA*. IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation. Sci Immunol. 2023 May 26;8(83):eade2335. doi: 10.1126/sciimmunol.ade2335. Epub 2023 May 26. PMID: 372356822. * = co-first authors, ** = co-senior authors

Lindell RB, Zhang D, Bush J, Wallace DC, Rabinowitz JD, Lu W, Wherry EJ, Weiss SL, Henrickson SE. Impaired Lymphocyte Responses in Pediatric Sepsis Vary by Pathogen Type and are Associated with Features of Immunometabolic Dysregulation. Shock. 2022 Jun 1;57(6):191-199. doi: 10.1097/SHK.0000000000001943.
PMID: 35759301

Trimodal single-cell profiling reveals a novel pediatric CD8αα+ T cell subset and broad age-related molecular reprogramming across the T cell compartment. Thomson Z, He Z, Swanson E, Henderson K, Phalen C, Zaim SR, Pebworth MP, Okada LY, Heubeck AT, Roll CR, Hernandez V, Weiss M, Genge PC, Reading J, Giles JR, Manne S, Dougherty J, Jasen CJ, Greenplate AR, Becker LA, Graybuck LT, Vasaikar SV, Szeto GL, Savage AK, Speake C, Buckner JH, Li XJ, Bumol TF, Wherry EJ, Torgerson TR, Vella LA, Henrickson SE, Skene PJ, Gustafson CE. Nat Immunol. 2023 Nov;24(11):1947-1959. doi: 10.1038/s41590-023-01641-8. Epub 2023 Oct 16.

Sayed S*, Diwadkar AR*, Dudley JW,* O’Brien J, Dvorin D, Kenyon CC, Himes BE**, Hill DA**, Henrickson SE**. COVID-19 Pandemic-Related Reductions in Pediatric Asthma Exacerbations Corresponded with an Overall Decrease in Respiratory Viral Infections. J Allergy Clin Immunol Pract. 2022 Jan;10(1):91-99.e12. doi: 10.1016/j.jaip.2021.10.067. Epub 2021 Nov 14. PMID: 34785388
* = co-first authors, ** = co-senior authors

Taquechel K*, Diwadkar AR*, Sayed S,* Dudley JW, Grundmeier RW, Kenyon C, Henrickson SE**, Himes BE**, Hill DA**. Pediatric Asthma Health Care Utilization, Viral Testing, and Air Pollution Changes During the COVID-19 Pandemic. 2020 Nov-Dec;8(10):3378-3387.e11. doi: 10.1016/j.jaip.2020.07.057.Epub 2020 Aug 20.
* = co-first authors, ** = co-senior authors

Virtue AT, McCright SJ, Wright JM, Jimenez MT, Mowel WK, Kotzin JJ, Joannas L, Basavappa MG, Spencer SP, Clark ML, Eisennagel SH, Williams A, Levy M, Manne S, Henrickson SE, Wherry EJ, Thaiss CA, Elinav E, Henao-Mejia J. The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs. Sci Transl Med (2019). 12:11(496). pii: eaav1892. doi: 10.1126/scitranslmed.aav1892.

Henrickson SE*, Manne S*, Dolfi DV, Mansfield KD, Parkhouse K, Mistry RD, Alpern ER, Hensley SE, Sullivan KE, Coffin SE, Wherry EJ. Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection. Cell Reports (2018). 22: 411-426. * = co-first authors

Henrickson SE, Perro M, Loughhead SM, Senman B, Stutte S, Quigley M, Alexe G, Iannacone M, Flynn MP, Omid S, Jesneck JL, Imam S, Mempel TR, Mazo IB, Haining WN, von Andrian UH. Antigen Availability Determines CD8+ T Cell-Dendritic Cell Interaction Kinetics and Memory Fate Decisions. Immunity (2013) 39: 496-507.

Henrickson SE, Mempel TR, Mazo IB, Artyomov MN, Zheng H, Liu B, Flynn M, Senman B, Junt T, Wong HC, Chakraborty AK, UH von Andrian. T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation. Nat. Immunol. (2008) 9: 282-291.

Mempel T, Henrickson SE and UH von Andrian. T-cell priming by Dendritic cells in Lymph Nodes Occurs in Three Distinct Phases. Nature. (2004) 427: 154-159.

RECENT REVIEW ARTICLES

Mauracher AA, Henrickson SE. Leveraging Systems Immunology to Optimize Diagnosis and Treatment of Inborn Errors of Immunity. Front Syst Biol. 2022;2:910243. doi: 10.3389/fsysb.2022.910243. Epub 2022 Jul 18.
PMID: 37670772

Campos JS, Henrickson SE. Defining and targeting patterns of T cell dysfunction in inborn errors of immunity. Front Immunol. 2022 Sep 14;13:932715. doi: 10.3389/fimmu.2022.932715. PMID: 36189259

Cohn IS, Henrickson SE, Striepen B, Hunter CA. Immunity to Cryptosporidium: Lessons from Acquired and Primary ImmunodeficienciesJ Immunol. 2022 Dec 15;209(12):2261-2268. doi: 10.4049/jimmunol.2200512.
PMID: 36469846 Free PMC article.

Fang X, Henao-Mejia J, Henrickson SE. Obesity and immune status in children. Curr Opin Pediatr. 2020 Dec;32(6):805-815. doi: 10.1097/MOP.0000000000000953. PMID: 33105275

Hay C, Henrickson SE. The impact of obesity on immune function in pediatric asthma. Curr Opin Allergy Clin Immunol. 2021 Apr 1;21(2):202-215. doi: 10.1097/ACI.0000000000000725.
PMID: 33620885