The Dermis Contains Langerin+ Dendritic Cells That Develop and Function Independently of Epidermal Langerhans Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2007 Dec 19

PMID 18086861

Citations 166

Authors

Lionel Franz Poulin

Sandrine Henri

Beatrice de Bovis

Elisabeth Devilard

Adrien Kissenpfennig

Bernard Malissen

Affiliations

Soon will be listed here.

Abstract

Langerhans cells (LCs) constitute a subset of dendritic cells (DCs) that express the lectin langerin and that reside in their immature state in epidermis. Paradoxically, in mice permitting diphtheria toxin (DT)-mediated ablation of LCs, epidermal LCs reappeared with kinetics that lagged behind that of their putative progeny found in lymph nodes (LNs). Using bone marrow (BM) chimeras, we showed that a major fraction of the langerin(+), skin-derived DCs found in LNs originates from a developmental pathway that is independent from that of epidermal LCs. This pathway, the existence of which was unexpected, originates in the dermis and gives rise to langerin(+) dermal DCs (DDCs) that should not be confused with epidermal LCs en route to LNs. It explains that after DT treatment, some langerin(+), skin-derived DCs reappear in LNs long before LC-derived DCs. Using CD45 expression and BrdU-labeling kinetics, both LCs and langerin(+) DDCs were found to coexist in wild-type mice. Moreover, DT-mediated ablation of epidermal LCs opened otherwise filled niches and permitted repopulation of adult noninflammatory epidermis with BM-derived LCs. Our results stress that the langerin(+) DC network is more complex than originally thought and have implications for the development of transcutaneous vaccines and the improvement of humanized mouse models.

Citing Articles

CD301b dendritic cell-derived IL-2 dictates CD4 T helper cell differentiation.

Tatsumi N, El-Fenej J, Davila-Pagan A, Kumamoto Y Nat Commun. 2025; 16(1):2002.

PMID: 40011469 PMC: 11865452. DOI: 10.1038/s41467-025-55916-9.

Ultraviolet Radiation-Induced Tolerogenic Dendritic Cells in Skin: Insights and Mechanisms.

Ghajar-Rahimi G, Yusuf N, Xu H Cells. 2025; 14(4).

PMID: 39996779 PMC: 11854269. DOI: 10.3390/cells14040308.

Monocytes give rise to Langerhans cells that preferentially migrate to lymph nodes at steady state.

Raquer-McKay H, Maqueda-Alfaro R, Saravanan S, Arroyo Hornero R, Clausen B, Gottfried-Blackmore A Proc Natl Acad Sci U S A. 2024; 121(47):e2404927121.

PMID: 39541348 PMC: 11588065. DOI: 10.1073/pnas.2404927121.

Langerhans cells regulate immunity in adulthood by regulating postnatal dermal lymphatic development.

Sim J, Bell R, Feng Z, Chyou S, Shipman W, Kataru R bioRxiv. 2024; .

PMID: 39071369 PMC: 11275746. DOI: 10.1101/2024.07.12.603312.

Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design.

Clemente B, Denis M, Silveira C, Schiavetti F, Brazzoli M, Stranges D Front Immunol. 2023; 14:1294929.

PMID: 38090568 PMC: 10711611. DOI: 10.3389/fimmu.2023.1294929.

References

Hladik F, Sakchalathorn P, Ballweber L, Lentz G, Fialkow M, Eschenbach D . Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity. 2007; 26(2):257-70. PMC: 1885958. DOI: 10.1016/j.immuni.2007.01.007. View

Steinman R, Nussenzweig M . Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci U S A. 2002; 99(1):351-8. PMC: 117564. DOI: 10.1073/pnas.231606698. View

Manz M . Human-hemato-lymphoid-system mice: opportunities and challenges. Immunity. 2007; 26(5):537-41. DOI: 10.1016/j.immuni.2007.05.001. View

Tripp C, Chang-Rodriguez S, Stoitzner P, Holzmann S, Stossel H, Douillard P . Ontogeny of Langerin/CD207 expression in the epidermis of mice. J Invest Dermatol. 2004; 122(3):670-2. DOI: 10.1111/j.0022-202X.2004.22337.x. View

Zhang M, Tang H, Guo Z, An H, Zhu X, Song W . Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol. 2004; 5(11):1124-33. DOI: 10.1038/ni1130. View

Blanpain C, Horsley V, Fuchs E . Epithelial stem cells: turning over new leaves. Cell. 2007; 128(3):445-58. PMC: 2408375. DOI: 10.1016/j.cell.2007.01.014. View

Kissenpfennig A, Ait-Yahia S, Clair-Moninot V, Stossel H, Badell E, Bordat Y . Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function. Mol Cell Biol. 2004; 25(1):88-99. PMC: 538791. DOI: 10.1128/MCB.25.1.88-99.2005. View

Kabashima K, Banks T, Ansel K, Lu T, Ware C, Cyster J . Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid tissue dendritic cells. Immunity. 2005; 22(4):439-50. DOI: 10.1016/j.immuni.2005.02.007. View

Bogunovic M, Ginhoux F, Wagers A, Loubeau M, Isola L, Lubrano L . Identification of a radio-resistant and cycling dermal dendritic cell population in mice and men. J Exp Med. 2006; 203(12):2627-38. PMC: 2118165. DOI: 10.1084/jem.20060667. View

10.

Wu L, Liu Y . Development of dendritic-cell lineages. Immunity. 2007; 26(6):741-50. DOI: 10.1016/j.immuni.2007.06.006. View

11.

Larregina A, Falo Jr L . Changing paradigms in cutaneous immunology: adapting with dendritic cells. J Invest Dermatol. 2005; 124(1):1-12. DOI: 10.1111/j.1523-1747.2004.23554.x. View

12.

Henri S, Vremec D, Kamath A, Waithman J, Williams S, Benoist C . The dendritic cell populations of mouse lymph nodes. J Immunol. 2001; 167(2):741-8. DOI: 10.4049/jimmunol.167.2.741. View

13.

Naik S, Metcalf D, Van Nieuwenhuijze A, Wicks I, Wu L, OKeeffe M . Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol. 2006; 7(6):663-71. DOI: 10.1038/ni1340. View

14.

Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y . Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity. 2000; 12(1):71-81. DOI: 10.1016/s1074-7613(00)80160-0. View

15.

Kamath A, Henri S, Battye F, Tough D, Shortman K . Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs. Blood. 2002; 100(5):1734-41. View

16.

Jung S, Unutmaz D, Wong P, Sano G, de Los Santos K, Sparwasser T . In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity. 2002; 17(2):211-20. PMC: 3689299. DOI: 10.1016/s1074-7613(02)00365-5. View

17.

Palframan R, Jung S, Cheng G, Weninger W, Luo Y, Dorf M . Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J Exp Med. 2001; 194(9):1361-73. PMC: 2195988. DOI: 10.1084/jem.194.9.1361. View

18.

Villadangos J, Schnorrer P . Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat Rev Immunol. 2007; 7(7):543-55. DOI: 10.1038/nri2103. View

19.

Kaplan D, Jenison M, Saeland S, Shlomchik W, Shlomchik M . Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity. Immunity. 2005; 23(6):611-20. DOI: 10.1016/j.immuni.2005.10.008. View

20.

de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong M, de Gruijl T . Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat Med. 2007; 13(3):367-71. DOI: 10.1038/nm1541. View