Insoo Kang, MD
ProfessorCards
Appointments
Additional Titles
Director of Allergy & Immunology, Internal Medicine
Contact Info
Appointments
Additional Titles
Director of Allergy & Immunology, Internal Medicine
Contact Info
Appointments
Additional Titles
Director of Allergy & Immunology, Internal Medicine
Contact Info
About
Titles
Professor
Director of Allergy & Immunology, Internal Medicine
Biography
Dr. Insoo Kang is Professor of Medicine (Rheumatology, Allergy & Immunology) at Yale University School of Medicine. He completed his post-graduate training in rheumatology and immunology research at Yale. He has been on the faculty at Yale School of Medicine since 1999. He is a physician scientist with a research interest in understanding the human immune system using biological samples and clinical data. In particular, Dr. Kang has defined subsets of T cells with distinct cellular characteristics based on the expression of cytokine receptors on T cells in health and disease as well as the interactions of such cell subsets with monocytes and other immune cells.
Appointments
Rheumatology
ProfessorPrimary
Other Departments & Organizations
- Allergy & Immunology
- Dean's Workshops
- Human and Translational Immunology Program
- Internal Medicine
- Interstitial Lung Disease (ILD) Program
- Rheumatic Diseases Research Core
- Rheumatology
- Rheumatology, Allergy, & Immunology
- Yale Center for Research on Aging (Y-Age)
- Yale Medicine
- Yale Stem Cell Center
- Yale Ventures
Education & Training
- Fellow
- Yale University School of Medicine (1997)
- Resident
- Yale Affiliated Program at Hospital of Saint Raphael (1994)
- MD
- Hallym University (1990)
Research
Overview
Studying the role of cytokine receptors and cytokines in defining human T cell subsets and regulating their functions in health and disease (aging and inflammation).
The cytokine IL-7 is essential for the homeostasis of memory T cells. We identified two novel subsets of effector memory (EM) CD8+ T cells with high and low levels of IL-7 receptor α chain expression (IL-7Rαhigh and low) in human peripheral blood. Compared to IL-7Rαhigh cells, IL-7Rαlow EM CD8+ T cells were highly antigen-experienced, cytotoxic and replication senescent cells.My lab found the expansion of IL-7Rαlow EM CD8+ T cells in older adults as well as in patients with SLE, which can be related to repetitive immune stimulations. Alternatively, but not mutually exclusive, the expansion of IL-7Rαlow EM CD8+ T cells could be driven by the cytokine IL-15 which is essentially involved in CD8+ T cell homeostasis.Also, we have found that DNA methylation, a mechanism involved in regulating gene expression, was responsible in part for conferring unique pro-inflammatory traits of IL-7Rαhigh and low EM CD8+ T cells.
While studying IL-7Rαhigh and low EM CD8+ T cells in human peripheral blood, my lab found a unique subset of EM CD8+ T cells that express high levels of IL-6Ra in addition to IL-7Rα.These cells that potently proliferated, survived, and produced high levels of the Th2-type cytokines IL-5 and IL-13 had increased levels of the transcription factor GATA3 in comparison to other EM CD8+ T cells.In fact, GATA3 was required for IL-6Rα expression. Patients with asthma, a Th2 response-related disease, had an increased frequency of IL-6Rαhigh EM CD8+ T cells in peripheral blood compared to healthy controls.Our study first identified human IL-6Rαhigh EM CD8+ T cells that may serve as a reservoir for effector CD8+ T cells, particularly the ones producing Th2-type cytokines.
Defining the role of IL-1β, its receptor and NLRP3 inflammasome in promoting Th17 cell response and inflammation in health and disease.
While conducting studies on CD8+ T cell in humans, my lab has investigated human CD4+ T cells in health and disease (e.g. SLE).This is particularly important given the dynamic interactions among different immune cells.T helper (Th) 17 cells are a recently identified subset of Th cells that produce the pro-inflammatory cytokine IL-17.In fact, we reported an increased frequency of Th17 cells that correlated with disease activity in patients with SLE.Cytokines such as IL-1β is essential for the development of Th17 cells.My lab identified a subset of CD4+ T cells with the expression of IL-1 receptor 1 (IL-1R1) that potently produced IL-17 in human naïve and memory CD4+ T cells.This work, which first showed a potential role for IL-1R1 as a molecule identifying Th17 cells in humans, was published in Blood and cited as a “Must Read” paper by Faculty of 1000 Biology.To find the possible mechanism for increased IL-17 production in lupus patients, we initiated a study on whether lupus target autoantigen and antibody immune complexes could activate human monocytes, a primary source of IL-1β, leading to the production of IL-1β which increases Th17 cell response.In fact, my lab has found that lupus autoimmune complexes of U1-snRNP and dsDNA could induce IL-1β from healthy human monocytes via activating the NLRP3 inflammasome, a multi-protein complex that cleaves pro-IL-1β into the active IL-1β.These studies first show the possible role of the caspase-1-containing NLRP3 inflammasome in the pathogenesis of lupus, providing a scientific rationale for targeting this molecular complex as tested in animal models of lupus.
Medical Research Interests
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Min Shin, PhD
Hong-Jai Park
Joseph Craft, MD
Junghee Jenny Shin, MD, PhD
Richard Bucala, MD, PhD
Ruth R Montgomery, PhD
Aging
T-Lymphocytes
Autoimmunity
Inflammation
Publications
2024
Expression of IL-7RαlowCX3CR1+ CD8+ T Cells and α4β7 Integrin Tagged T Cells Related to Mucosal Immunity in Children with Inflammatory Bowel Disease
Yang D, Kim H, Dinh D, Yang J, Hyun C, Jee Y, Lee N, Shin M, Kang I, Kang K. Expression of IL-7RαlowCX3CR1+ CD8+ T Cells and α4β7 Integrin Tagged T Cells Related to Mucosal Immunity in Children with Inflammatory Bowel Disease. Pediatric Gastroenterology Hepatology & Nutrition 2024, 27: 345-354. PMID: 39563840, PMCID: PMC11570351, DOI: 10.5223/pghn.2024.27.6.345.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsPeripheral blood mononuclear cellsCD4<sup>+</sup> T cellsInflammatory bowel diseaseT cellsUlcerative colitis groupCrohn's disease groupEffector memoryColitis groupControl groupEffector memory CD8<sup>+</sup> T cellsMemory CD8<sup>+</sup> T cellsCD8+ T cellsBowel diseaseEM CD8<sup>+</sup> T cellsTrafficking immune cellsDisease groupPathogenesis of ulcerative colitisBlood mononuclear cellsInflamed intestinal mucosaConcentrations of TNF-aIntestinal mucosaSerum levelsT lymphocytesImmune cellsRelationship of MicroRNA according to Immune Components of Breast Milk in Korean Lactating Mothers
Choi Y, Lee D, Song J, Kim K, Min H, Chung S, Kim T, Kim C, Kang I, Lee N, Yi D. Relationship of MicroRNA according to Immune Components of Breast Milk in Korean Lactating Mothers. Pediatric Gastroenterology Hepatology & Nutrition 2024, 27: 322-331. PMID: 39319280, PMCID: PMC11419785, DOI: 10.5223/pghn.2024.27.5.322.Peer-Reviewed Original ResearchPrognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma
Valdez C, Sánchez-Zuno G, Osmani L, Ibrahim W, Galan A, Bacchiocchi A, Halaban R, Kulkarni R, Kang I, Bucala R, Tran T. Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma. Oncotarget 2024, 15: 507-520. PMID: 39028303, PMCID: PMC11259151, DOI: 10.18632/oncotarget.28615.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsMeSH KeywordsAdultAgedAged, 80 and overAntigens, Differentiation, B-LymphocyteBiomarkers, TumorFemaleHistocompatibility Antigens Class IIHumansImmune Checkpoint InhibitorsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMelanomaMiddle AgedMutationPrognosisRetrospective StudiesSkin NeoplasmsConceptsMacrophage migration inhibitory factorImmune checkpoint inhibitionD-dopachrome tautomeraseExpression of macrophage migration inhibitory factorDrivers of tumor progressionInflammatory cell markersPatient tumor samplesPatient survival outcomesMigration inhibitory factorStatistically significant differenceCheckpoint inhibitionImmune therapyPrognostic valueSurvival outcomesResistant melanomaGene expressionImproved survivalRetrospective studyInflammatory markersTumor progressionCell markersTumor samplesClinical evidenceMelanomaBulk RNA sequencingPOS1390 SINGLE-CELL PROFILING IDENTIFIES PERIPHERAL IMMUNE SIGNATURE OF CORONARY ARTERY DISEASE IN SLE PATIENTS
LI C, Osmani L, Gu J, Zhao H, Kang I, Bucala R, Dong X. POS1390 SINGLE-CELL PROFILING IDENTIFIES PERIPHERAL IMMUNE SIGNATURE OF CORONARY ARTERY DISEASE IN SLE PATIENTS. 2024, 929.2-929. DOI: 10.1136/annrheumdis-2024-eular.412.Peer-Reviewed Original ResearchIL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination
Park H, Shin M, Shin J, Kim H, Kang B, Par-Young J, Unlu S, Afinogenova Y, Catanzaro J, Young J, Kim M, Lee S, Jeon S, You S, Racke M, Bucala R, Kang I. IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination. EBioMedicine 2024, 103: 105114. PMID: 38640835, PMCID: PMC11041015, DOI: 10.1016/j.ebiom.2024.105114.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsCD4<sup>+</sup> T cellsCOVID-19 mRNA vaccinesAntigen-specific CD4<sup>+</sup> T cell responsesT cell responsesPrimary antibody deficiencyCD4<sup>+</sup> T cell responsesT cellsIL-1R1MRNA vaccinesIL-1IgG antibodiesAntigen-specific CD4<sup>+</sup> T cellsCD4+ T cell responsesLevels of IL-1R1Human CD4<sup>+</sup> T cellsIL-1 receptor 1Healthy individualsDose of COVID-19 mRNA vaccineAntigen-specific CD4IL-1R1 expressionT cell immunityRepetitive antigenic stimulationCytokines interleukin (IL)-1Immune response to virusesExpression of IL-1R1
2023
Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease
Young J, Park H, Kim M, Par-Young J, Bartlett H, Kim H, Unlu S, Osmani L, Shin M, Bucala R, van Dyck C, Allore H, Mecca A, You S, Kang I. Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease. Immunity & Ageing 2023, 20: 71. PMID: 38042785, PMCID: PMC10693128, DOI: 10.1186/s12979-023-00396-y.Peer-Reviewed Original ResearchCitationsAltmetricConceptsPeripheral bloodT cellsAlzheimer's diseaseEM CD8Memory CD8Gene signatureAge-related immune changesIL-7 receptor alphaEffector memory CD8Strong risk factorT cell expansionAD genesAge-associated expansionImmune changesRisk factorsCD8Dementia patientsIL-7RNeuropsychological testingReceptor alphaNeurocognitive functionRT-qPCR resultsDisease severityPatientsNormal personsNatural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus
Yang M, Lam T, Kanyo J, Kang I, Zhou Z, Clarke S, Mamula M. Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus. Autoimmunity 2023, 56: 2282945. PMID: 37994408, PMCID: PMC10897934, DOI: 10.1080/08916934.2023.2282945.Peer-Reviewed Original ResearchAltmetricModulating IL-1β and its receptors shapes spike-specific CD4 +T cell responses to mRNA vaccination
Park H, Shin M, Shin J, Kim H, Kang B, Par-Young J, Unlu S, Afinogenova Y, Catanzaro J, Young J, Kim M, Lee S, You S, Racke M, Bucala R, Kang I. Modulating IL-1β and its receptors shapes spike-specific CD4 +T cell responses to mRNA vaccination. The Journal Of Immunology 2023, 210: 159.20-159.20. DOI: 10.4049/jimmunol.210.supp.159.20.Peer-Reviewed Original ResearchConceptsCOVID-19 mRNA vaccinesT cellsIL-1βIL-1R2MRNA vaccinesIL-1 receptor 1IL-1R1 expressionIL-1R2 expressionSpike-specific CD4Vaccine-induced CD4T cell immunityT cell responsesSpecific antibody productionMRNA vaccinationCell immunityDurable immunityIL-1R1IL-1BCD4Healthy individualsQuest DiagnosticsAntibody productionCell responsesReceptor 1Receptor systemChanges in microRNAs during Storage and Processing of Breast Milk
Kim J, Kim K, Min H, Lee E, Lim I, Song J, Kang I, Yi D. Changes in microRNAs during Storage and Processing of Breast Milk. Metabolites 2023, 13: 139. PMID: 36837760, PMCID: PMC9963775, DOI: 10.3390/metabo13020139.Peer-Reviewed Original ResearchCitationsAltmetric
2022
Implication of IL-7 receptor alpha chain expression by CD8+ T cells and its signature in defining biomarkers in aging
Shin M, Park H, Young J, Kang I. Implication of IL-7 receptor alpha chain expression by CD8+ T cells and its signature in defining biomarkers in aging. Immunity & Ageing 2022, 19: 66. PMID: 36544153, PMCID: PMC9768896, DOI: 10.1186/s12979-022-00324-6.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricConceptsT cellsImmune agingHost defenseIL-7 receptor alpha chainFrequencies of naïveT cell subsetsAlpha chain expressionAssociation of CD8Age-associated conditionsReceptor alpha chainMemory CD8Treatment of illnessCell subsetsInflammatory disordersIL-7RαCD8High riskImmune functionTherapeutic interventionsImmune systemPotential biomarkersGene signatureChain expressionOlder adultsBiomarkers
Clinical Trials
Current Trials
Yale Rheumatology Program Patient Registry and Bio-Repository
HIC ID2000026608REGRoleSub InvestigatorPrimary Completion Date06/01/2030Recruiting ParticipantsGenderBothAge18 years - 99 yearsYale Lupus and Connective Tissue Disease Bio-Repository / Yale Rheumatology Bio-Repository
HIC ID1602017276REGRoleSub InvestigatorPrimary Completion Date06/30/2036Recruiting ParticipantsGenderBothAge18+ years
Academic Achievements & Community Involvement
activity Connective Tissue Disease
ResearchDetails01/01/2008 - PresentSouth KoreaAbstract/SynopsisDr. Insoo Kang is collaborating with Section of Rheumatology at Catholic University of Korea on T-cell immunity in connective tissue diseases.
News
News
- February 26, 2024
Elise Liu Receives 2024 AAAAI Foundation Faculty Development Award
- June 13, 2023
Shin Awarded Immune Deficiency Foundation Grant
- April 20, 2023
Fellow Focus in Four: Lais Osmani, MD, Rheumatology
- November 02, 2022
How A Common Gene Variant Influences Your Risk of Severe Illness From COVID-19