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          Labs @ NIAMS
          Cutaneous Leukocyte Biology Section








Cutaneous Leukocyte Biology Section


Keisuke (Chris) Nagao, M.D., Ph.D. FacebookEmailPrintFacebookEmail
        HF and immune cells

      Overview

                                  Senior Investigator
      
  


Keisuke (Chris) Nagao, M.D., Ph.D.
      
  


            keisuke.nagao@nih.gov
      
                                                                        

  
   Research Areas (IRP Lab Groups)
          Clinical Research,
          Computational Biology,
          Immunology,
          Microbiology and Infectious Diseases,
          Skin Biology,
          Virology
                                
            Mammalian skin is inhabited by various microbial communities known collectively as the microbiota. The host provides a home and nutrients for the microbes, and the microbes are crucial for stimulating healthy immunity, representing a mutually beneficial relationship. When this relationship changes, it may lead to perpetuating inflammation.

The Cutaneous Leukocyte Biology Section aims to understand how skin functions as an immune organ and studies mechanisms that underlie host-microbial symbiosis during health and disease, in both experimental models and human diseases.

Mechanisms of immune regulation and host-microbial symbiosis in the skin

Hair follicles are fascinating structures that produce hair. The laboratory has established hair follicles as immunologically functional structures that recruit and control the localization of immune cells through the production of chemokines and cytokines. In turn, immune cells, such as the innate lymphoid cells, control sebaceous gland function to tune the balance of the microbiota during homeostasis.

*Staphylococcus aureus*. While the contribution of *S. aureus* in eczematous inflammation has long been debated, the laboratory has demonstrated *S. aureus* to be a crucial driver of inflammation.

Dissecting pathological inflammation directly in human diseases

Advances in sequencing technologies, such as single-cell RNA sequencing, has enabled us to understand transcriptome at the single-cell level. These technologies provide us with opportunities to understand human diseases at unprecedented resolutions. The laboratory utilizes single-cell RNA sequencing and bioinformatics approaches to understand disease pathophysiology directly in humans and to understand how the immune system regulates the microbiota. Diseases of interest include, but are not limited to, severe drug hypersensitivities and primary immunodeficiencies.
      

                                            Related NIAMS LabsCutaneous Development and Carcinogenesis SectionCutaneous Microbiome and Inflammation SectionDermatology Consultation Service
  Scientific Advances
      
  

      July 11, 2023Macrophages Control Skin Susceptibility to a Common Bacterial Infection

                                                      Core Research Facilities

Labs at the NIAMS are supported by the following state-of-the-art facilities and services:

Biodata Mining and Discovery
	Flow Cytometry
	Genomic Technology
	Laboratory Animal Care and Use
	Light Imaging
	Translational Immunology

                                    Staff
                            
            **Keisuke (Chris) Nagao, M.D., Ph.D.**Senior Investigatorkeisuke.nagao@nih.gov
    **Otgonzaya Ayush, M.D., Ph.D.**Special Volunteerzaya.ayush@nih.gov
    **Baishakhi Ghosh, M.Sc., Ph.D.**Research Fellowbaishakhi.ghosh@nih.gov
    **Shubham Goel, Ph.D.**Research Fellowshubham.goel@nih.gov
    **Paul Kim, B.S.**Postbaccalaureate Fellowpaul.kim3@nih.gov
    **Keiko Sakamoto, M.D., Ph.D.**Stephen I. Katz Scholarkeiko.sakamoto@nih.gov
    **Akiko Sekiguchi, M.D., Ph.D.**Postdoctoral Fellow (Visiting)akiko.sekiguchi@nih.gov
            
                                                Image & Media Gallery
              
            Ben's Last Day (2020)
Ben's Last Day (2020)
        ×
      Ben's last day
    Cutaneous Leukocyte Biology Section, Holiday (2018)
Cutaneous Leukocyte Biology Section, Holiday (2018)
        ×
      The lab staff at the holidays
    Cutaneous Leukocyte Biology Section (2018)
Cutaneous Leukocyte Biology Section (2018)
        ×
      Photo of the team in the lab
    Cutaneous Leukocyte Biology Section Group
Cutaneous Leukocyte Biology Section Group
        ×
      Cutaneous Leukocyte Biology Section Group
    Cutaneous Leukocyte Biology Section (2016)
Cutaneous Leukocyte Biology Section (2016)
        ×
      Lab staff in an atrium
    Staphylococcus aureus drives atopic skin inflammation
Staphylococcus aureus drives atopic skin inflammation
        ×
      Illustration of normal skin alongside inflamed skin
        *Staphylococcus aureus* drives atopic skin inflammation (Kobayashi et al., 2015 Immunity. PMID: 25902485)
    Hair follicles provide IL-7 and IL-15 for skin-resident memory T cells
Hair follicles provide IL-7 and IL-15 for skin-resident memory T cells
        ×
      Visualization of hair follicles
        Hair follicles provide IL-7 and IL-15 for skin-resident memory T cells during homeostasis and lymphoma (Adachi et al., 2015 Nature Medicine. PMID: 26479922)
    Innate Lymphoid Cells in Hair Follicles
Innate Lymphoid Cells in Hair Follicles
        ×
      Visualizations and figures illustrating sebaceous glands.
        Innate lymphoid cells regulate sebaceous gland function to tune the balance of skin microbiota (Kobayashi et al., 2019 Cell. PMID: 30712873 )
    Single-cell RNA sequencing in inflamed skin
Single-cell RNA sequencing in inflamed skin
        ×
      Graphical plots of single-cell RNA-seq and identification of activated JAK-STAT pathway
        Utilization of single-cell RNA-seq to guide targeted therapy in a drug hypersensitivity syndrome (Kim et al., 2020 Nature Medicine. PMID: 31959990)
            
                                    Career Opportunities
              
      Stephen I. Katz Scholars in Dermatologic Research
      
  

      We are seeking individuals interested in a career in dermatology clinical and translational research. Trainees who have completed accredited rheumatology or dermatology training programs are eligible to apply for this program. Applications will be considered on a rolling basis.

    
      Program Details
              Postdoctoral Fellows
      
  

      Postdoctoral fellows interested in integrating bioinformatics and immunology to study basic and translational skin immunology should send a cover letter, curriculum vitae with bibliography, and the names and contact information for three references to Dr. Nagao.
            
                        
                                    Scientific Publications
              Selected Recent Publications
                  
      Distinct use of super-enhancer elements controls cell type-specific CD25 transcription and function.

    Spolski R, Li P, Chandra V, Shin B, Goel S, Sakamoto K, Liu C, Oh J, Ren M, Enomoto Y, West EE, Christensen SM, Wan ECK, Ge M, Lin JX, Yan B, Kazemian M, Yu ZX, Nagao K, Vijayanand P, Rothenberg EV, Leonard WJ
        

                    Sci Immunol.
        
                    2023 Nov 3;
        
                    8(89).
        
                    doi: 10.1126/sciimmunol.adi8217
                            PMID: 37922339
              Updates in SJS/TEN: collaboration, innovation, and community.

    Marks ME, Botta RK, Abe R, Beachkofsky TM, Boothman I, Carleton BC, Chung WH, Cibotti RR, Dodiuk-Gad RP, Grimstein C, Hasegawa A, Hoofnagle JH, Hung SI, Kaffenberger B, Kroshinsky D, Lehloenya RJ, Martin-Pozo M, Micheletti RG, Mockenhaupt M, Nagao K, Pakala S, Palubinsky A, Pasieka HB, Peter J, Pirmohamed M, Reyes M, Saeed HN, Shupp J, Sukasem C, Syu JY, Ueta M, Zhou L, Chang WC, Becker P, Bellon T, Bonnet K, Cavalleri G, Chodosh J, Dewan AK, Dominguez A, Dong X, Ezhkova E, Fuchs E, Goldman J, Himed S, Mallal S, Markova A, McCawley K, Norton AE, Ostrov D, Phan M, Sanford A, Schlundt D, Schneider D, Shear N, Shinkai K, Tkaczyk E, Trubiano JA, Volpi S, Bouchard CS, Divito SJ, Phillips EJ
        

                    Front Med (Lausanne).
        
                    2023;
        
                    10().
        
                    doi: 10.3389/fmed.2023.1213889
                            PMID: 37901413
              Mouse Models for Atopic Dermatitis.

    Sakamoto K, Nagao K
        

                    Curr Protoc.
        
                    2023 Mar;
        
                    3(3).
        
                    doi: 10.1002/cpz1.709
                            PMID: 36971661
              The Double-Stranded RNA Analog, Poly(I:C), Triggers Distinct Transcriptomic Shifts in Keratinocyte Subsets.

    Sakamoto K, Nagao K
        

                    J Invest Dermatol.
        
                    2022 Oct;
        
                    142(10).
        
                    doi: 10.1016/j.jid.2022.03.015
                            PMID: 35395221
              Flow cytometry analysis of the subpopulations of mouse keratinocytes and skin immune cells.

    Sakamoto K, Goel S, Funakoshi A, Honda T, Nagao K
        

                    STAR Protoc.
        
                    2022 Mar 18;
        
                    3(1).
        
                    doi: 10.1016/j.xpro.2021.101052
                            PMID: 34977690
              Neutrophils initiate and exacerbate Stevens-Johnson syndrome and toxic epidermal necrolysis.

    Kinoshita M, Ogawa Y, Hama N, Ujiie I, Hasegawa A, Nakajima S, Nomura T, Adachi J, Sato T, Koizumi S, Shimada S, Fujita Y, Takahashi H, Mizukawa Y, Tomonaga T, Nagao K, Abe R, Kawamura T
        

                    Sci Transl Med.
        
                    2021 Jun 30;
        
                    13(600).
        
                    doi: 10.1126/scitranslmed.aax2398
                            PMID: 34193610
              Cell-autonomous FLT3L shedding via ADAM10 mediates conventional dendritic cell development in mouse spleen.

    Fujita K, Chakarov S, Kobayashi T, Sakamoto K, Voisin B, Duan K, Nakagawa T, Horiuchi K, Amagai M, Ginhoux F, Nagao K
        

                    Proc Natl Acad Sci U S A.
        
                    2019 Jul 16;
        
                    116(29).
        
                    doi: 10.1073/pnas.1818907116
                            PMID: 31262819
              Choreographing Immunity in the Skin Epithelial Barrier.

    Kobayashi T, Naik S, Nagao K
        

                    Immunity.
        
                    2019 Mar 19;
        
                    50(3).
        
                    doi: 10.1016/j.immuni.2019.02.023
                            PMID: 30893586
              Langerhans Cells Prevent Autoimmunity via Expansion of Keratinocyte Antigen-Specific Regulatory T Cells.

    Kitashima DY, Kobayashi T, Woodring T, Idouchi K, Doebel T, Voisin B, Adachi T, Ouchi T, Takahashi H, Nishifuji K, Kaplan DH, Clausen BE, Amagai M, Nagao K
        

                    EBioMedicine.
        
                    2018 Jan;
        
                    27().
        
                    doi: 10.1016/j.ebiom.2017.12.022
                            PMID: 29307572
              ADAM17-Deficient Mice Model the Transcriptional Signature of Human Atopic Dermatitis.

    Woodring T, Kobayashi T, Kim D, Nagao K
        

                    J Invest Dermatol.
        
                    2018 Oct;
        
                    138(10).
        
                    doi: 10.1016/j.jid.2018.04.021
                            PMID: 29751002
              Langerhans Cells - The Macrophage in Dendritic Cell Clothing.

    Doebel T, Voisin B, Nagao K
        

                    Trends Immunol.
        
                    2017 Nov;
        
                    38(11).
        
                    doi: 10.1016/j.it.2017.06.008
                            PMID: 28720426
              Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome.

    Ouchi T, Kubo A, Yokouchi M, Adachi T, Kobayashi T, Kitashima DY, Fujii H, Clausen BE, Koyasu S, Amagai M, Nagao K
        

                    J Exp Med.
        
                    2011 Dec 19;
        
                    208(13).
        
                    doi: 10.1084/jem.20111718
                            PMID: 22143886
                
                                Key Publications
                  
            Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin.
    Voisin B, Nadella V, Doebel T, Goel S, Sakamoto K, Ayush O, Jo JH, Kelly MC, Kobayashi T, Jiang JX, Hu Y, Yan C, Nagao K
                    Immunity.
                    2023 Jul 11;
                    56(7).
                    doi: 10.1016/j.immuni.2023.06.006
                            PMID: 37402364

Disruption of the endopeptidase ADAM10-Notch signaling axis leads to skin dysbiosis and innate lymphoid cell-mediated hair follicle destruction.

    Sakamoto K, Jin SP, Goel S, Jo JH, Voisin B, Kim D, Nadella V, Liang H, Kobayashi T, Huang X, Deming C, Horiuchi K, Segre JA, Kong HH, Nagao K
        Immunity.
        2021 Sep 22;
        pii: S1074-7613(21)00364-2. doi: 10.1016/j.immuni.2021.09.001
        PMID: 34582748

Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: a case report.

    Kim D, Kobayashi T, Voisin B, Jo JH, Sakamoto K, Jin SP, Kelly M, Pasieka HB, Naff JL, Meyerle JH, Ikpeama ID, Fahle GA, Davis FP, Rosenzweig SD, Alejo JC, Pittaluga S, Kong HH, Freeman AF, Nagao K
        Nat Med.
        2020 Feb;
        26(2).
        doi: 10.1038/s41591-019-0733-7
        PMID: 31959990

Homeostatic Control of Sebaceous Glands by Innate Lymphoid Cells Regulates Commensal Bacteria Equilibrium.

    Kobayashi T, Voisin B, Kim DY, Kennedy EA, Jo JH, Shih HY, Truong A, Doebel T, Sakamoto K, Cui CY, Schlessinger D, Moro K, Nakae S, Horiuchi K, Zhu J, Leonard WJ, Kong HH, Nagao K
    
        Cell.
        2019 Feb 21;
        176(5).
    
        doi: 10.1016/j.cell.2018.12.031
        PMID: 30712873

Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma.

    Adachi T, Kobayashi T, Sugihara E, Yamada T, Ikuta K, Pittaluga S, Saya H, Amagai M, Nagao K
        
            Nat Med.
            2015 Nov;
            21(11).
        
            doi: 10.1038/nm.3962
                    PMID: 26479922

Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis.

    Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, Kong HH, Amagai M, Nagao K
        
            Immunity.
            2015 Apr 21;
            42(4).
        
            doi: 10.1016/j.immuni.2015.03.014
                    PMID: 25902485

Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin.

    Nagao K, Kobayashi T, Moro K, Ohyama M, Adachi T, Kitashima DY, Ueha S, Horiuchi K, Tanizaki H, Kabashima K, Kubo A, Cho YH, Clausen BE, Matsushima K, Suematsu M, Furtado GC, Lira SA, Farber JM, Udey MC, Amagai M
        
            Nat Immunol.
            2012 Jun 24;
            13(8).
        
            doi: 10.1038/ni.2353
                    PMID: 22729248 
                            See all Publications on PubMed
            
                                    News & Highlights
              
            Spotlight on Research | December 13, 2021
Researchers identify cellular pathway that regulates inflammatory hair loss
NIH researchers reveal new insights about the relationship between hair and hair follicles and the skin’s immune system.
Read More
    | April 5, 2019
NIAMS Investigators Elected to the American Society for Clinical Investigation
Congratulations to Drs. Isaac Brownell, Heidi Kong, and Chris Nagao who were elected to the American Society for Clinical Investigation!
Read More



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        Last Updated: February 2024
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