Interleukin 15 Skews Monocyte Differentiation into Dendritic Cells with Features of Langerhans Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2001 Oct 3

PMID 11581322

Citations 80

Authors

M Mohamadzadeh

F Berard

G Essert

C Chalouni

B Pulendran

J Davoust

G Bridges

A K Palucka

J Banchereau

Affiliations

Soon will be listed here.

Abstract

Langerhans cells (LCs) represent a subset of immature dendritic cells (DCs) specifically localized in the epidermis and other mucosal epithelia. As surrounding keratinocytes can produce interleukin (IL)-15, a cytokine that utilizes IL-2Rgamma chain, we analyzed whether IL-15 could skew monocyte differentiation into LCs. Monocytes cultured for 6 d with granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-15 differentiate into CD1a(+)HLA-DR(+)CD14(-)DCs (IL15-DCs). Agents such as lipopolysaccharide (LPS), tumor necrosis factor (TNF)alpha, and CD40L induce maturation of IL15-DCs to CD83(+), DC-LAMP(+) cells. IL15-DCs are potent antigen-presenting cells able to induce the primary (mixed lymphocyte reaction [MLR]) and secondary (recall responses to flu-matrix peptide) immune responses. As opposed to cultures made with GM-CSF/IL-4 (IL4-DCs), a proportion of IL15-DCs expresses LC markers: E-Cadherin, Langerin, and CC chemokine receptor (CCR)6. Accordingly, IL15-DCs, but not IL4-DCs, migrate in response to macrophage inflammatory protein (MIP)-3alpha/CCL20. However, IL15-DCs cannot be qualified as "genuine" Langerhans cells because, despite the presence of the 43-kD Langerin, they do not express bona fide Birbeck granules. Thus, our results demonstrate a novel pathway in monocyte differentiation into dendritic cells.

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References

Vincent J, Vandenabeele S, Vanbervliet B, Pin J, Patel S, Mattei M . A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon DC maturation, is transiently expressed in MHC class II compartment. Immunity. 1998; 9(3):325-36. DOI: 10.1016/s1074-7613(00)80615-9. View

Yang D, Howard O, Chen Q, Oppenheim J . Cutting edge: immature dendritic cells generated from monocytes in the presence of TGF-beta 1 express functional C-C chemokine receptor 6. J Immunol. 1999; 163(4):1737-41. View

Ito T, Inaba M, Inaba K, Toki J, Sogo S, Iguchi T . A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells. J Immunol. 1999; 163(3):1409-19. View

Waldmann T, Tagaya Y . The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu Rev Immunol. 1999; 17:19-49. DOI: 10.1146/annurev.immunol.17.1.19. View

Lodolce J, Boone D, Chai S, Swain R, Dassopoulos T, Trettin S . IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity. 1998; 9(5):669-76. DOI: 10.1016/s1074-7613(00)80664-0. View

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

Kennedy M, Glaccum M, Brown S, Butz E, Viney J, Embers M . Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med. 2000; 191(5):771-80. PMC: 2195858. DOI: 10.1084/jem.191.5.771. View

Ku C, Murakami M, Sakamoto A, Kappler J, Marrack P . Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science. 2000; 288(5466):675-8. DOI: 10.1126/science.288.5466.675. View

Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu Y . Immunobiology of dendritic cells. Annu Rev Immunol. 2000; 18:767-811. DOI: 10.1146/annurev.immunol.18.1.767. View

10.

Berard F, Blanco P, Davoust J, Neidhart-Berard E, Nouri-Shirazi M, Taquet N . Cross-priming of naive CD8 T cells against melanoma antigens using dendritic cells loaded with killed allogeneic melanoma cells. J Exp Med. 2000; 192(11):1535-44. PMC: 2193101. DOI: 10.1084/jem.192.11.1535. View

11.

Caux C, Dezutter-Dambuyant C, Schmitt D, Banchereau J . GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature. 1992; 360(6401):258-61. DOI: 10.1038/360258a0. View

12.

Tang A, Amagai M, Granger L, Stanley J, Udey M . Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature. 1993; 361(6407):82-5. DOI: 10.1038/361082a0. View

13.

Mohamadzadeh M, Takashima A, DOUGHERTY I, Knop J, Bergstresser P, Cruz Jr P . Ultraviolet B radiation up-regulates the expression of IL-15 in human skin. J Immunol. 1995; 155(9):4492-6. View

14.

Edelbaum D, Mohamadzadeh M, Bergstresser P, Sugamura K, Takashima A . Interleukin (IL)-15 promotes the growth of murine epidermal gamma delta T cells by a mechanism involving the beta- and gamma c-chains of the IL-2 receptor. J Invest Dermatol. 1995; 105(6):837-43. DOI: 10.1111/1523-1747.ep12326630. View

15.

Strobl H, Riedl E, Scheinecker C, Pickl W, Rappersberger K, Majdic O . TGF-beta 1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors. J Immunol. 1996; 157(4):1499-507. View

16.

Caux C, Vanbervliet B, Massacrier C, Dezutter-Dambuyant C, Jacquet C, Yoneda K . CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF+TNF alpha. J Exp Med. 1996; 184(2):695-706. PMC: 2192705. DOI: 10.1084/jem.184.2.695. View

17.

Mohamadzadeh M, McGuire M, DOUGHERTY I, Cruz Jr P . Interleukin-15 expression by human endothelial cells: up-regulation by ultraviolet B and psoralen plus ultraviolet A treatment. Photodermatol Photoimmunol Photomed. 1996; 12(1):17-21. DOI: 10.1111/j.1600-0781.1996.tb00238.x. View

18.

Borkowski T, Letterio J, Farr A, Udey M . A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: the skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells. J Exp Med. 1996; 184(6):2417-22. PMC: 2196398. DOI: 10.1084/jem.184.6.2417. View

19.

Greaves D, Wang W, Dairaghi D, Dieu M, Rossi D, Caux C . CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3alpha and is highly expressed in human dendritic cells. J Exp Med. 1997; 186(6):837-44. PMC: 2199049. DOI: 10.1084/jem.186.6.837. View

20.

Geissmann F, Prost C, Monnet J, Dy M, Brousse N, Hermine O . Transforming growth factor beta1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J Exp Med. 1998; 187(6):961-6. PMC: 2212193. DOI: 10.1084/jem.187.6.961. View