About

Sarah Henrickson, M.D., Ph.D., is an Assistant Professor of Pediatrics specializing in Allergy and Immunology at the Children's Hospital of Philadelphia. Her clinical expertise includes immune deficiency and asthma, while her research focuses on human immunology and immune dysregulation. Her work involves studying mouse models of disease, primary immune deficiency, and asthma, with a particular interest in immune response mechanisms and immune system disorders. She completed her undergraduate degree in Biochemical Sciences at Harvard College, graduating summa cum laude in 2001. She earned her Ph.D. in Immunology from Harvard Medical School in 2008 and her M.D. from Harvard Medical School in 2011. Her research contributions include investigating the genomic circuitry underlying immunological responses to pediatric respiratory infections, T cell sensing of antigen dose, and immune system development at the single-cell level. Her work has been recognized in the field of immunology, including being highlighted as a New Hot Paper by Thomson ISI.

Research topics

• Medicine
• Immunology
• Internal medicine
• Virology
• Biology
• Pathology
• Genetics
• Environmental health

Selected publications

• Follicular Helper T Cells and B Cell Maturation in Patients with 22q11.2 Deletion Syndrome and Recurrent Infections

  Journal of Clinical Immunology · 2026-02-03 · 2 citations

  articleOpen access

  PURPOSE: 22q11.2 Deletion Syndrome has been primarily described as a disorder of T cell production secondary to thymic hypoplasia. However, there is great complexity in the clinical picture with infections, autoimmunity, and inflammation occurring. Emerging evidence suggests that qualitative T cell dysfunction occurs, and the goal of this study was to utilize single-cell RNA-seq to better define altered gene expression patterns to inform on the mechanisms associated with recurrent infections. METHODS: We utilized single-cell RNA-seq to define distinct populations in 22q11.2 Deletion Syndrome (N = 13) and controls (N = 11) as well as within a subcohort of patients with 22q11.2 Deletion Syndrome and recurrent infections. RESULTS: When we analyzed differentially expressed genes, we identified a signature of type I interferons across all cell types. Within the T cell compartment, and particularly within the follicular helper T cells, we identified a senescence signature. The alterations found in T cells were most substantial in the patients with recurrent infection. CONCLUSIONS: While T cell numbers can often normalize in patients with 22q11.2 Deletion Syndrome, our data indicate significantly altered function as defined by differentially expressed genes and aligned with what is known about T cell senescence. The effect was greatest in the patients with recurrent infection. This would be expected to impact T cell function and may account for ongoing symptoms, reduced B cell maturation, and possibly the risk of immune dysregulation.

  PublisherDOI

• Author Correction: Multi-omic profiling reveals age-related immune dynamics in healthy adults

  Nature · 2026-04-10

  articleOpen access
  PublisherOA PDFDOI

• T cell dysregulation and remodeling in pediatric obesity and weight loss

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-21

  articleOpen accessSenior authorCorresponding

  Obesity is a chronic inflammatory disease associated with immune dysregulation. However, alterations in adaptive immune function remain unclear, particularly in the setting of childhood obesity and weight loss. We defined peripheral T cell dysregulation in a cross-sectional cohort of pediatric participants across weight categories and in a longitudinal cohort of adolescents with severe obesity undergoing bariatric surgery. We found increased expression of activation markers (including PD-1 and CD69) in non-naive CD8+ T cells whereas non-naive CD4+ T cells were skewed towards Tfh, Th17, and mixed Th2/Th17 populations. Consistent with a hyperactive state, T cells had enhanced capacity for inflammatory cytokine production (including IFN-γ and TNF-α) along with enrichment of gene sets associated with cytokine signaling, cell proliferation, and cell death across. Notably, these phenotypic, functional, and transcriptional alterations were not fully resolved after bariatric surgery, despite clinically meaningful weight loss. Together, these findings demonstrate that pediatric obesity leads to dysregulation of adaptive immune function with incomplete normalization after weight loss.

  PublisherDOI

• Arterial Catheter-Associated Proximal Ischemic Injury in Critically Ill Children: Evidence of Endothelial Dysfunction and Immune Dysregulation

  Pediatric Critical Care Medicine · 2026-03-13

  articleOpen access

  OBJECTIVES: Arterial catheter-associated proximal ischemic injury (ACAPII) is a rare but serious complication in critically ill pediatric patients who require arterial access. In a cohort of critically ill children with multiple organ dysfunction syndrome (MODS), we investigated proteomic differences in children who developed ACAPII with the aim of identifying mechanistic pathways that may contribute to the pathogenesis of this complication. We hypothesized that the plasma proteome at MODS onset would differ between children who later develop ACAPII and those who do not. DESIGN: Single-center cohort study of pediatric patients with MODS defined by modified Proulx criteria who underwent arterial catheter placement. We obtained plasma samples within 48 hours of MODS onset. Grading of ACAPII was completed by the hospital vascular access team using standardized criteria. Proteomic analysis was performed using Olink proximity extension assay. Gene set enrichment analysis was used to identify mechanistic pathways enriched in ACAPII cases. SETTING: Single-center academic PICU. PATIENTS: Pediatric patients with MODS and arterial access at Children's Hospital of Philadelphia from January 2020 to December 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five of 66 (7.6%) MODS patients with arterial access developed ACAPII. Age, severity of illness, and organ dysfunction profiles did not differ between injured and noninjured patients. Six pathways of immune dysregulation, involving Signal Transducer and Activator of Transcription signaling and cytokine-mediated apoptosis, were enriched in patients with ACAPII ( p < 0.0001). Five pathways associated with endothelial dysfunction were also significantly altered in ACAPII patients ( p < 0.0001). Differential expression analysis identified 18 plasma proteins associated with injury after adjustment for age and severity of illness (false discovery rate p < 0.05), supporting the hypothesis that endothelial injury and immune dysregulation may contribute to ACAPII pathogenesis. CONCLUSIONS: In a small pediatric cohort, we identified pathways of immune dysregulation and endothelial dysfunction associated with ACAPII. Because these factors precede ACAPII, there may be a window for treatment.

  PublisherOA PDFDOI

• 37: DYSREGULATED STAT3 SIGNALING DEFINES A TARGETABLE, HIGH-MORTALITY SUBPHENOTYPE OF PEDIATRIC SEPSIS

  Critical Care Medicine · 2025-01-01

  articleSenior author
  PublisherDOI

• 847: ENDOTHELIAL DAMAGE AND IMMUNE DYSREGULATION ARE ASSOCIATED WITH ARTERIAL LINE INJURIES IN CHILDREN

  Critical Care Medicine · 2025-01-01

  article
  PublisherDOI

• Targeting Complex Cutaneous Viral Infections in Search of Inborn Errors of Immunity

  Acta Dermato Venereologica · 2025-06-09

  articleOpen access

  Inborn errors of immunity are rare diseases and 50-80% present with dermatological manifestations. This study evaluated difficult-to-treat cutaneous human papillomavirus infections and their associations with immunological defects. Patients were recruited from the Dermatological Outpatient Clinic over 2 years. Patients reporting persistent common warts and/or a combination of molluscum contagiosum or more than 2 flat warts, with a clinical assessment of severe or persistent skin infection, met the clinical severity criteria for inclusion. Resistance to several therapies was also considered. A total of 632 patient records were analysed to clinically characterize the warts, laboratory data, treatments used and their responses, comorbidities, and family history. Among these, 459 cases were initially excluded from further evaluation. A questionnaire was provided by phone to 173 patients, among whom 47 patients were selected for an in-person consultation. Of these, 6 met the criteria for further evaluation. Immunological tests revealed neutropenia, low levels of immunoglobulin isotypes (IgA, IgM, and IgG), and reduced frequency of lymphocyte subsets. Family history, flat warts, and associated recurrent viral infections suggested the need for further immunological evaluation. Criteria are proposed for identifying patients with cutaneous warts that warrant additional evaluation for potential inborn errors of immunity.

  PublisherOA PDFDOI

• Longitudinal multi-omic immune profiling of the healthy pediatric immune system and its response to vaccination 3300

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description Investigations of human immune responses typically focus on adults, resulting in limited knowledge of the pediatric immune system and how it responds to distinct challenges early in life. To bridge this gap, we conducted a 3-year longitudinal multi-omic profiling study of 46 healthy children aged 11-13 as they received flu, HPV, DTaP, and COVID vaccines. This dataset includes scRNAseq of &amp;gt; 3.5 million PBMCs classified into 70 immune cell types based on our Immune Health Atlas, as well as plasma proteomics and high-dimensional flow cytometry. We are utilizing this dataset to characterize the pediatric immune system at baseline and in response to acute and chronic challenges as it compares to the adult immune system, with the ability to compare neoantigen and recall responses within the same children. This analysis revealed age-independent and age-dependent response patterns, with similar cellular compositions and gene-expression changes characterizing response to chronic CMV infection between children and adults but heightened activity in specific cell types responding to flu vaccination in children. We also identified increased activity in specific cell types in response to vaccines that elicit recall as opposed to neoantigen responses, providing a means to understand how immune memory is established and re-engaged in children. These initial findings lay the groundwork upon which we can build and deepen our understanding of immune dynamics in early adolescence. Topic Categories Vaccines and Immunotherapy (VAC)

  PublisherOA PDFDOI

• Multi-omic profiling reveals age-related immune dynamics in healthy adults

  Nature · 2025-10-29 · 33 citations

  articleOpen access

  The generation and maintenance of immunity is a dynamic process that is dependent on age1–3. Here, to better understand its progression, we profiled peripheral immunity in more than 300 healthy adults (25 to 90 years of age) using single-cell RNA sequencing, proteomics and flow cytometry, following 96 adults longitudinally across 2 years with seasonal influenza vaccination. The resulting resource generated a single-cell RNA-sequencing dataset of more than 16 million peripheral blood mononuclear cells with 71 immune cell subsets from our Human Immune Health Atlas and enabled us to interrogate how immune cell composition and states shift with age, chronic viral infection and vaccination. From these data, we demonstrate robust, non-linear transcriptional reprogramming in T cell subsets with age that is not driven by systemic inflammation or chronic cytomegalovirus infection. This age-related reprogramming led to a functional T helper 2 (TH2) cell bias in memory T cells that is linked to dysregulated B cell responses against highly boosted antigens in influenza vaccines. Collectively, this study reveals unique features of the immune ageing process that occur prior to advanced age and provides novel targets for age-related immune modulation. We provide interactive tools for exploring this extensive human immune health resource at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ . This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

  PublisherOA PDFDOI

• Multimodal analysis defines <i>GNG4</i> as a distinguishing feature of germinal center-positioned CD4 T follicular helper cells in humans

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-13 · 1 citations

  preprintOpen access

  Abstract CD4 T follicular helper (Tfh) cells coordinate humoral immune responses within germinal centers (GC) of lymphoid tissue. Despite their critical roles in vaccination and autoimmunity, the gene expression programs that define functionally distinct human Tfh states— and the molecular pathways engaged by Tfh positioned within the GC niche—remain incompletely understood. This gap has limited translational efforts to monitor or therapeutically target specific Tfh states for clinical benefit. Here, we delineate human CD4 T cell heterogeneity in tonsils and peripheral blood using trimodal single-cell sequencing and spectral flow cytometry to define epigenomic, transcriptional, and proteomic features of distinct Tfh states. Tfh with a GC-like phenotype exhibited markedly increased chromatin accessibility and both mRNA and protein expression of G protein subunit gamma 4 ( GNG4) . In tonsil, single-cell spatial transcriptomics defined GNG4 expression as a distinguishing feature of activated Tfh states within spatially demarcated GC compartments, with greater specificity than conventionally GC-associated features such as BCL6, TOX2, and S1PR2 . In contrast, GNG4 − Tfh primarily localized to nonGC regions and exhibited a resting, Th17-polarized phenotype. Together, these data highlight GNG4 as a central feature of activated, GC-positioned Tfh cell identity in humans. One Sentence Summary GNG4 expression defines activated CD4 T follicular helper cells localized to the germinal center of human lymphoid tissue.

  PublisherDOI

Recent grants

• Obesity dysregulates immune and metabolic status in asthma and alters infection susceptibility.

  NIH · $935k · 2018–2023

Frequent coauthors

• E. John Wherry

  University of Pennsylvania

  116 shared

• Jean‐Laurent Casanova

  Université Paris Cité

  102 shared

• Laura A. Vella

  Children's Hospital of Philadelphia

  90 shared

• Laurent Abel

  Université Paris Cité

  85 shared

• David T. Teachey

  Children's Hospital of Philadelphia

  70 shared

• Edward M. Behrens

  Children's Hospital of Philadelphia

  68 shared

• Caroline Diorio

  Children's Hospital of Philadelphia

  60 shared

• YL Lau

  University of Hong Kong

  60 shared

Labs

• Sarah Henrickson LabPI