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. 

The laboratory utilizes a variety of experimental models to understand how host-microbe relationships are maintained and disrupted. In particular, the laboratory has generated a mouse model for atopic dermatitis that recapitulates the susceptibility of atopic dermatitis patients to skin colonization of 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.

Image & Media Gallery

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.

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;
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).
doi: 10.3389/fmed.2023.1213889
PMID: 37901413

Mouse Models for Atopic Dermatitis.

Sakamoto K, Nagao K
Curr Protoc.
2023 Mar;
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;
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;
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;
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;
doi: 10.1073/pnas.1818907116
PMID: 31262819

Choreographing Immunity in the Skin Epithelial Barrier.

Kobayashi T, Naik S, Nagao K
2019 Mar 19;
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
2018 Jan;
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;
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;
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;
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
2023 Jul 11;
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
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;
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
2019 Feb 21;
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;
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
2015 Apr 21;
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;
doi: 10.1038/ni.2353
PMID: 22729248

News & Highlights

Spotlight on Research |

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.

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!