Overview

Principal Investigator

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

Dr. Nagao’s research focuses on cellular and molecular mechanisms that regulate immunological and structural homeostasis in the skin.

The Cutaneous Leukocyte Biology Section studies the mutual crosstalk that occur between the skin, the microbiota and resident leukocytes during steady-state and inflammation. Recent studies include the identification of hair follicles as immunological organs that support the skin-tropism of leukocytes via chemokine and cytokine production. The lab has also generated a mouse model for atopic dermatitis that spontaneously develop eczematous lesions and exhibit naturally occurring dysbiosis, which was utilized to demonstrate Staphylococcus aureus as a critical element during eczema formation. Current focus of the lab is to investigate microbiota-tissue-innate leukocyte crosstalk that maintain immunological and structural homeostasis.

  1. Leukocyte-stromal crosstalk

    It has become clearer over the recent years that the skin harbors varieties of resident leukocytes. However, the mechanisms that govern skin immune homeostasis are not well known. We previously discovered the hair follicles activate immunity in response to physical trauma by producing chemokines that recruit skin dendritic cells to perturbed sites. Extending this work, we have more recently identified that hair follicles produce T cell homeostatic cytokines that play critical roles in the cutaneous persistence of non-malignant and malignant skin resident T cells.  We currently focus on resident innate cells in the skin to understand their fundamental roles in mediating immunological and structural homeostasis.
  2. Regulation of the skin microbiota

    With a plethora of bacterial communities that reside on its surface, the skin represents the outermost immunological interface of our body. Understanding of how the microbiota-host crosstalk is regulated (or disrupted) is crucial to ultimately control immune responses that occur in skin, particularly in atopic dermatitis (AD). Staphyloccus aureus colonization is universal in AD and common in epidermal growth factor receptor (EGFR) inhibitor-treated patients, but the cause-or-effect relationship of S. aureus and eczema had been a matter of debate. We have developed a mouse model for AD with naturally occurring dysbiosis and eczema formation and showed that S. aureus is critical during eczema formation, providing an answer to a longstanding clinical question. The lab currently investigates how innate cells may regulate the skin microbiota during steady-state and inflammation.

Image & Media Gallery

Scientific Publications

 

 

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

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
The Journal of investigative dermatology.
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 in immunology.
2017 Nov;
38(11).
doi: 10.1016/j.it.2017.06.008
PMID: 28720426

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
Nature medicine.
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
Nature immunology.
2012 Jun 24;
13(8).
doi: 10.1038/ni.2353
PMID: 22729248

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
The Journal of experimental medicine.
2011 Dec 19;
208(13).
doi: 10.1084/jem.20111718
PMID: 22143886
Last Updated: May 2020