TY - JOUR
T1 - Nonredundant roles of keratinocyte-derived IL-34 and neutrophil-derived CSF1 in Langerhans cell renewal in the steady state and during inflammation
AU - Wang, Yaming
AU - Bugatti, Mattia
AU - Ulland, Tyler K.
AU - Vermi, William
AU - Gilfillan, Susan
AU - Colonna, Marco
N1 - Funding Information:
We would like to thank I. Kang and K. Choi for the assistance in embryo isolation and Y. Abu-Amer for providing Csf1op/op mice. Y.W. is supported by Lilly Innovation Fellowship Award (Eli Lilly and Company). M.B. is supported by Fondazione Beretta (Brescia, Italy). T.K.U. is supported by T32 training grant from NCI (5T32CA009547-30).M.C. is supported by NIH R21 AI105728 and the Alvin J. Siteman Cancer Research Fund (No. 09-FY14-01). Y.W. designed, performed, analyzed experiments, and wrote the manuscript; M.B. and W.V. carried out immunohistochemical analysis; T.K.U. performed BM transplant. S.G. generated the UBC-Cre/ERT2.Il34Flox/LacZ mice and set up timed-mating experiments; and M.C. supervised the research and wrote the manuscript.
Funding Information:
We would like to thank I. Kang and K. Choi for the assistance in embryo isolation and Y. Abu-Amer for providing Csf1op/op mice. Y.W. is supported by Lilly Innovation Fellowship Award (Eli Lilly and Company). M.B. is supported by Fondazione Beretta (Brescia, Italy). T.K.U. is supported by T32 training grant from NCI (5T32CA009547-30).M.C. is supported by NIH R21 AI105728 and the Alvin J. Siteman Cancer Research Fund (No. 09-FY14-01). Y.W. designed, performed, analyzed experiments, and wrote the manuscript; M.B. and W.V. carried out immunohistochemical analysis; T.K.U. performed BM transplant. S.G. generated the UBC-Cre/ERT2.Il34Flox/LacZ mice and set up timed-mating experiments; and M.C. supervised the research and wrote the manuscript.
Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - IL-34 and colony-stimulating factor 1 (CSF1) are two alternative ligands for the CSF1 receptor that play nonredundant roles in the development, survival, and function of tissue macrophages and Langerhans cells (LCs). In this study, we investigated the spatio-temporal production of IL-34 and its impact on skin LCs in the developing embryo and adult mice in the steady state and during inflammation using Il34LacZ reporter mice and newly generated inducible Il34-knockout mice. We found that IL-34 is produced in the developing skin epidermis of the embryo, where it promotes the final differentiation of LC precursors. In adult life, LCs required IL-34 to continually self-renew in the steady state. However, during UV-induced skin damage, LC regeneration depended on neutrophils infiltrating the skin, which produced large amounts of CSF1. We conclude that LCs require IL-34 when residing in fully differentiated and anatomically intact skin epidermis, but rely on neutrophil-derived CSF1 during inflammation. Our demonstration that neutrophils are an important source of CSF1 during skin inflammation may exemplify a mechanism through which neutrophils promote their subsequent replacement with mononuclear phagocytes.
AB - IL-34 and colony-stimulating factor 1 (CSF1) are two alternative ligands for the CSF1 receptor that play nonredundant roles in the development, survival, and function of tissue macrophages and Langerhans cells (LCs). In this study, we investigated the spatio-temporal production of IL-34 and its impact on skin LCs in the developing embryo and adult mice in the steady state and during inflammation using Il34LacZ reporter mice and newly generated inducible Il34-knockout mice. We found that IL-34 is produced in the developing skin epidermis of the embryo, where it promotes the final differentiation of LC precursors. In adult life, LCs required IL-34 to continually self-renew in the steady state. However, during UV-induced skin damage, LC regeneration depended on neutrophils infiltrating the skin, which produced large amounts of CSF1. We conclude that LCs require IL-34 when residing in fully differentiated and anatomically intact skin epidermis, but rely on neutrophil-derived CSF1 during inflammation. Our demonstration that neutrophils are an important source of CSF1 during skin inflammation may exemplify a mechanism through which neutrophils promote their subsequent replacement with mononuclear phagocytes.
KW - CSF1
KW - Cell development
KW - Cytokines
KW - IL-34
KW - Inflammation langerhans cells
UR - http://www.scopus.com/inward/record.url?scp=84959367081&partnerID=8YFLogxK
U2 - 10.1002/eji.201545917
DO - 10.1002/eji.201545917
M3 - Article
C2 - 26634935
AN - SCOPUS:84959367081
SN - 0014-2980
VL - 46
SP - 552
EP - 559
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 3
ER -