Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that continues to impose significant physical, mental, and economic burdens on patients. Recent research has suggested the significant role of tissueresident memory (TRM) cells in AD. However, the precise role and mechanisms of action of TRM cells in AD remain unclear. A deeper understanding of the involvement of TRM cells in AD will unveil promising pathways for future innovative therapeutic strategies. Methods: To investigate the involvement of TRM cells in AD, we used diverse mouse models and employed experimental techniques to manipulate cell formation and depletion. We assessed the inflammatory response by analyzing mouse ear phenotype, measuring ear thickness, and performing hematoxylin and eosin staining. Flow cytometry and immunofluorescence staining were used to identify different cell types and evaluate changes in cell quantity. Additionally, we used qPCR to analyze gene expression of relevant chemokines and cytokines. Results: Our study revealed the presence of TRM cells in the skin after exposure to calcipotriol. After a 24-h rechallenge, we observed substantial neutrophil infiltration into the previously irritated skin. Neutrophil depletion prior to re-challenge effectively prevented early flare-up responses during AD recurrence. Furthermore, we demonstrate that CD4+TRM cells upregulate expression of cytokines INF-gamma and TNF-alpha, which may induce the expression of CXCL1, thereby recruiting neutrophils and contributing to the chronic recurrent inflammation observed in AD. Conclusions: We have established a novel, chronic recurrent mouse model for investigating TRM cells in AD. Our findings demonstrate that CD4+TRM cells in the skin mediate early flare-up response during AD recurrence and influence the chronic recurrent inflammation of AD by recruiting neutrophils. Targeting CD4+TRM cells may represent a promising approach for the treatment of chronic recurrent inflammation in AD.
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21PLUS, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Kim, S.
Park, C.
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机构:
Brigham & Womens Hosp, Dermatol, 75 Francis St, Boston, MA 02115 USAYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Park, C.
Shin, J.
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机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Shin, J.
Noh, J.
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h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Noh, J.
Kim, H.
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h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Kim, H.
Kim, J.
论文数: 0引用数: 0
h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21PLUS, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Kim, J.
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机构:
Lee, H.
Lee, J.
论文数: 0引用数: 0
h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Lee, J.
Kupper, T. S.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dermatol, 75 Francis St, Boston, MA 02115 USAYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Naidoo, Karmella
Jagot, Ferdinand
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Jagot, Ferdinand
van den Elsen, Lieke
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New Zealand
Univ Western Australia, Sch Mol Sci, Crawley, AustraliaMalaghan Inst Med Res, Wellington, New Zealand
van den Elsen, Lieke
Pellefigues, Christophe
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Pellefigues, Christophe
Jones, Angela
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Jones, Angela
Luo, Huijun
论文数: 0引用数: 0
h-index: 0
机构:
Mayo Clin, Div Pulm Med, Dept Biochem & Mol Biol, Scottsdale, AZ USAMalaghan Inst Med Res, Wellington, New Zealand
Luo, Huijun
Johnston, Karen
论文数: 0引用数: 0
h-index: 0
机构:
GlycoSyn, Lower Hutt, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Johnston, Karen
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机构:
Painter, Gavin
Roediger, Ben
论文数: 0引用数: 0
h-index: 0
机构:
Centenary Inst, Newtown, NSW, AustraliaMalaghan Inst Med Res, Wellington, New Zealand
Roediger, Ben
Lee, James
论文数: 0引用数: 0
h-index: 0
机构:
Mayo Clin, Div Pulm Med, Dept Biochem & Mol Biol, Scottsdale, AZ USAMalaghan Inst Med Res, Wellington, New Zealand
Lee, James
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机构:
Weninger, Wolfgang
Le Gros, Graham
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Le Gros, Graham
Forbes-Blom, Elizabeth
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New Zealand
Nestle Res Ctr, Lausanne, SwitzerlandMalaghan Inst Med Res, Wellington, New Zealand
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Kim, Brian S.
Siracusa, Mark C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Siracusa, Mark C.
Rak, Gregory D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Rak, Gregory D.
Kubo, Masato
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN, Yokohama Inst, Res Ctr Integrat Med Sci, Lab Cytokine Regulat, Yokohama, Kanagawa, Japan
Tokyo Univ Sci, Res Inst Biomed Sci, Div Mol Pathol, Chiba, JapanUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Kubo, Masato
Moghaddam, Amin E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, EnglandUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Moghaddam, Amin E.
Sattentau, Quentin A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, EnglandUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Sattentau, Quentin A.
Comeau, Michael R.
论文数: 0引用数: 0
h-index: 0
机构:
Amgen Inc, Inflammat Res, Seattle, WA USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Comeau, Michael R.
Spergel, Jonathan M.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Philadelphia, Dept Pediat, Div Allergy & Immunol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Spergel, Jonathan M.
Artis, David
论文数: 0引用数: 0
h-index: 0
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA
Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21PLUS, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Kim, S.
Park, C.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dermatol, 75 Francis St, Boston, MA 02115 USAYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Park, C.
Shin, J.
论文数: 0引用数: 0
h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Shin, J.
Noh, J.
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h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Noh, J.
Kim, H.
论文数: 0引用数: 0
h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Kim, H.
Kim, J.
论文数: 0引用数: 0
h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21PLUS, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Kim, J.
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机构:
Lee, H.
Lee, J.
论文数: 0引用数: 0
h-index: 0
机构:
Yonsei Univ, Coll Med, Dermatol, Seoul, South KoreaYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
Lee, J.
Kupper, T. S.
论文数: 0引用数: 0
h-index: 0
机构:
Brigham & Womens Hosp, Dermatol, 75 Francis St, Boston, MA 02115 USAYonsei Univ, Coll Med, Dermatol, Seoul, South Korea
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Naidoo, Karmella
Jagot, Ferdinand
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Jagot, Ferdinand
van den Elsen, Lieke
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New Zealand
Univ Western Australia, Sch Mol Sci, Crawley, AustraliaMalaghan Inst Med Res, Wellington, New Zealand
van den Elsen, Lieke
Pellefigues, Christophe
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Pellefigues, Christophe
Jones, Angela
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Jones, Angela
Luo, Huijun
论文数: 0引用数: 0
h-index: 0
机构:
Mayo Clin, Div Pulm Med, Dept Biochem & Mol Biol, Scottsdale, AZ USAMalaghan Inst Med Res, Wellington, New Zealand
Luo, Huijun
Johnston, Karen
论文数: 0引用数: 0
h-index: 0
机构:
GlycoSyn, Lower Hutt, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Johnston, Karen
论文数: 引用数:
h-index:
机构:
Painter, Gavin
Roediger, Ben
论文数: 0引用数: 0
h-index: 0
机构:
Centenary Inst, Newtown, NSW, AustraliaMalaghan Inst Med Res, Wellington, New Zealand
Roediger, Ben
Lee, James
论文数: 0引用数: 0
h-index: 0
机构:
Mayo Clin, Div Pulm Med, Dept Biochem & Mol Biol, Scottsdale, AZ USAMalaghan Inst Med Res, Wellington, New Zealand
Lee, James
论文数: 引用数:
h-index:
机构:
Weninger, Wolfgang
Le Gros, Graham
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New ZealandMalaghan Inst Med Res, Wellington, New Zealand
Le Gros, Graham
Forbes-Blom, Elizabeth
论文数: 0引用数: 0
h-index: 0
机构:
Malaghan Inst Med Res, Wellington, New Zealand
Nestle Res Ctr, Lausanne, SwitzerlandMalaghan Inst Med Res, Wellington, New Zealand
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Kim, Brian S.
Siracusa, Mark C.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Siracusa, Mark C.
Rak, Gregory D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Rak, Gregory D.
Kubo, Masato
论文数: 0引用数: 0
h-index: 0
机构:
RIKEN, Yokohama Inst, Res Ctr Integrat Med Sci, Lab Cytokine Regulat, Yokohama, Kanagawa, Japan
Tokyo Univ Sci, Res Inst Biomed Sci, Div Mol Pathol, Chiba, JapanUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Kubo, Masato
Moghaddam, Amin E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, EnglandUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Moghaddam, Amin E.
Sattentau, Quentin A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, EnglandUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Sattentau, Quentin A.
Comeau, Michael R.
论文数: 0引用数: 0
h-index: 0
机构:
Amgen Inc, Inflammat Res, Seattle, WA USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Comeau, Michael R.
Spergel, Jonathan M.
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp Philadelphia, Dept Pediat, Div Allergy & Immunol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Spergel, Jonathan M.
Artis, David
论文数: 0引用数: 0
h-index: 0
机构:
Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA
Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USAUniv Penn, Dept Microbiol, Philadelphia, PA 19104 USA