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.
- 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.
- 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.
Kobayashi T, Voisin B, Kim DY, Kennedy E, Jo JH, Shih HY, Truong A, Sakamoto K, Doebel T, Cui CY, Schlessinger D, Moro K, Nakae S, Zhu J, Leonard WJ, Kong HH, Nagao K*. Homeostatic control of sebaceous glands by innate lymphoid cells regulate commensal bacteria equilibrium. Cell, 176(5):982-997, 2019. *Corresponding author.
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*. Langerhans cells prevent autoimmunity via expansion of keratinocyte antigen-specific regulatory T cells, EBioMedicine, 27:293-303, 2018. *Corresponding author.
Woodring T, Kobayashi T, Kim D, Nagao K*. ADAM17-Deficient Mice Model the Transcriptional Signature of Human Atopic Dermatitis. Journal of Investigative Dermatology, 138(10):2283-2286, 2018. *Corresponding author.
Doebel T, Voisin B, Nagao K*. Langerhans Cells – The Macrophage in Dendritic Cell Clothing, 2017, Trends in Immunology, 38(11) 817-828. *Corresponding author.
Adachi T, Kobayashi T, Sugihara E, Yamada T, Ikuta K, Pittaluga S, Saya H, Amagai M, Nagao K*. Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma, 2015, Nature Medicine. 11: 1272-9, 2015. *Corresponding author.
Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, Kong HH, Amagai M, Nagao K*. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis, Immunity. 42(4) 756-766, 2015. *Corresponding author.
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, and Amagai M. Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin. Nature Immunology: 13 (8) 744-752, 2012 *Corresponding author.
Ouchi T, Kubo A, Yokouchi M, Adachi T, Kobayashi T, Kitashima DY, Fujii H, Clausen BE, Koyasu S, Amagai M, and Nagao K*. Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome. The Journal of Experimental Medicine: 208 (13) 2607-13, 2011 *Corresponding author.