Integrin α5 regulates motility of human monocyte‐derived Langerhans cells during immune response

Author:

Guo Zhihan1,Murakami Masato12,Saito Kaori134ORCID,Kato Hiroko14ORCID,Toriyama Manami145ORCID,Tominaga Makoto678ORCID,Ishii Ken J.49ORCID,Fujita Fumitaka134

Affiliation:

1. Graduate School of Pharmaceutical Sciences Osaka University Osaka Japan

2. Skin Care Institute Mandom Corporation Osaka Japan

3. Advanced Technology Institute Mandom Corporation Osaka Japan

4. Center for Vaccine and Adjuvant Research National Institutes of Biomedical Innovation, Health and Nutrition Osaka Japan

5. Graduate School of Science and Technology Nara Institute of Science and Technology Nara Japan

6. Exploratory Research Center on Life and Living Systems National Institutes of Natural Sciences Okazaki Japan

7. National Institute for Physiological Sciences National Institutes of Natural Sciences Okazaki Japan

8. Department of Physiological Sciences Sokendai (The Graduate University for Advanced Studies) Okazaki Japan

9. Division of Vaccine Science, The Institute of Medical Science The University of Tokyo Tokyo Japan

Abstract

AbstractLangerhans cells (LCs) are mainly present in the epidermis and mucosa, and have important roles during skin infection. Migration of LCs to lymph nodes is essential for antigen presentation. However, due to the difficulties in isolating and culturing human LCs, it is not fully understood how LCs move and interact with the extracellular matrix (ECM) through their adhesion molecules such as integrin, during the immune responses. In this study, we aimed to investigate LC motility, cell shape and the role of integrin under inflammatory conditions using monocyte‐derived Langerhans cells (moLCs) as a model. As a result, lipopolysaccharide (LPS) stimulation increased adhesion on fibronectin coated substrate and integrin α5 expression in moLCs. Time‐lapse imaging of moLCs revealed that stimulation with LPS elongated cell shape, whilst decreasing their motility. Additionally, this decrease in motility was not observed when pre‐treated with a neutralising antibody targeting integrin α5. Together, our data suggested that activation of LCs decreases their motility by promoting integrin α5 expression to enhance their affinity to the fibronectin, which may contribute to their migration during inflammation.

Funder

Japan Agency for Medical Research and Development

Publisher

Wiley

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