Bone Marrow-Derived Dendritic Cell Cultures from RAG Mice Include IFN-γ-Producing NK Cells

Overview

Journal Immunohorizons

Specialty Allergy & Immunology

Date 2020 Jul 16

PMID 32665300

Citations 6

Authors

Kaveh Abdi

L Michael Thomas

Karen Laky

Mehrnoosh Abshari

Polly Matzinger

Eric O Long

Affiliations

Soon will be listed here.

Abstract

Dendritic cells (DCs) play a key role in the initiation of an immune response and are known as "professional" APCs because of their ability to activate naive T cells. A widely used method to generate DCs in vitro is to culture bone marrow (BM) cells or blood monocytes in the presence of GM-CSF and IL-4. In this study, we show that a small population of NK cells residing in the BM of RAG, but not RAG γ chain mice, remain in the DC culture and is the source of IFN-γ produced after stimulation with LPS. These cells, which may represent early promoters of LPS-induced responses, have to be taken into account when interpreting experiments using BM-derived DCs.

Citing Articles

Myeloid antigen-presenting cells in neurodegenerative diseases: a focus on classical and non-classical MHC molecules.

Afify R, Lipsius K, Wyatt-Johnson S, Brutkiewicz R Front Neurosci. 2024; 18:1488382.

PMID: 39720231 PMC: 11667120. DOI: 10.3389/fnins.2024.1488382.

Immunomodulatory effects of nanoparticles on dendritic cells in a model of allergic contact dermatitis: importance of PD-L2 expression.

Wong Lau A, Perez Pineda J, DeLouise L Sci Rep. 2023; 13(1):15992.

PMID: 37749142 PMC: 10520013. DOI: 10.1038/s41598-023-42797-5.

Immunomodulatory Effects of Nanoparticles on Dendritic Cells in a Model of Allergic Contact Dermatitis - Importance of PD-L2 Expression.

Wong Lau A, Perez Pineda J, DeLouise L Res Sq. 2023; .

PMID: 37503107 PMC: 10371126. DOI: 10.21203/rs.3.rs-3069059/v1.

Guidelines for mouse and human DC generation.

Lutz M, Ali S, Audiger C, Autenrieth S, Berod L, Bigley V Eur J Immunol. 2022; 53(11):e2249816.

PMID: 36303448 PMC: 10704271. DOI: 10.1002/eji.202249816.

Dendritic cells Trigger IFN-γ secretion by NK cells independent of IL-12 and IL-18.

Abdi K, Laky K, Abshari M, Hill E, Lantz L, Singh N Eur J Immunol. 2022; 52(9):1431-1440.

PMID: 35816444 PMC: 10608798. DOI: 10.1002/eji.202149733.

References

Helft J, Bottcher J, Chakravarty P, Zelenay S, Huotari J, Schraml B . GM-CSF Mouse Bone Marrow Cultures Comprise a Heterogeneous Population of CD11c(+)MHCII(+) Macrophages and Dendritic Cells. Immunity. 2015; 42(6):1197-211. DOI: 10.1016/j.immuni.2015.05.018. View

Abdi K, Singh N, Matzinger P . T-cell control of IL-12p75 production. Scand J Immunol. 2006; 64(2):83-92. DOI: 10.1111/j.1365-3083.2006.01767.x. View

Becker T, Coley S, Wherry E, Ahmed R . Bone marrow is a preferred site for homeostatic proliferation of memory CD8 T cells. J Immunol. 2005; 174(3):1269-73. DOI: 10.4049/jimmunol.174.3.1269. View

Belilos E, Diamond B, Carsons S . TNF in combination with GM-CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages. J Leukoc Biol. 1992; 52(3):274-81. View

Ohteki T, Suzue K, Maki C, Ota T, Koyasu S . Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response. Nat Immunol. 2001; 2(12):1138-43. DOI: 10.1038/ni729. View

Sallusto F, Lanzavecchia A . Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994; 179(4):1109-18. PMC: 2191432. DOI: 10.1084/jem.179.4.1109. View

Di Rosa F, Santoni A . Bone marrow CD8 T cells are in a different activation state than those in lymphoid periphery. Eur J Immunol. 2002; 32(7):1873-80. DOI: 10.1002/1521-4141(200207)32:7<1873::AID-IMMU1873>3.0.CO;2-P. 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

Lassila O, Vainio O, Matzinger P . Can B cells turn on virgin T cells?. Nature. 1988; 334(6179):253-5. DOI: 10.1038/334253a0. View

10.

Abdi K, Singh N, Matzinger P . Lipopolysaccharide-activated dendritic cells: "exhausted" or alert and waiting?. J Immunol. 2012; 188(12):5981-9. PMC: 3370068. DOI: 10.4049/jimmunol.1102868. View

11.

Steinman R . The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991; 9:271-96. DOI: 10.1146/annurev.iy.09.040191.001415. View

12.

Palucka K, Banchereau J, Mellman I . Designing vaccines based on biology of human dendritic cell subsets. Immunity. 2010; 33(4):464-78. PMC: 2975953. DOI: 10.1016/j.immuni.2010.10.007. View

13.

Erlich Z, Shlomovitz I, Edry-Botzer L, Cohen H, Frank D, Wang H . Macrophages, rather than DCs, are responsible for inflammasome activity in the GM-CSF BMDC model. Nat Immunol. 2019; 20(4):397-406. DOI: 10.1038/s41590-019-0313-5. View

14.

Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S . Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992; 176(6):1693-702. PMC: 2119469. DOI: 10.1084/jem.176.6.1693. View

15.

Mellman I, Turley S, Steinman R . Antigen processing for amateurs and professionals. Trends Cell Biol. 1998; 8(6):231-7. DOI: 10.1016/s0962-8924(98)01276-8. View

16.

Abdi K, Laky K, Padhan K, Petrovas C, Skinner J, Kabat J . Cutting Edge: Quantitative Determination of CD40L Threshold for IL-12 and IL-23 Production from Dendritic Cells. J Immunol. 2018; 201(10):2879-2884. PMC: 6215252. DOI: 10.4049/jimmunol.1800721. View

17.

Shinkai Y, Rathbun G, Lam K, Oltz E, Stewart V, Mendelsohn M . RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992; 68(5):855-67. DOI: 10.1016/0092-8674(92)90029-c. View

18.

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

19.

Karo J, Schatz D, Sun J . The RAG recombinase dictates functional heterogeneity and cellular fitness in natural killer cells. Cell. 2014; 159(1):94-107. PMC: 4371485. DOI: 10.1016/j.cell.2014.08.026. View

20.

Colucci F, Soudais C, Rosmaraki E, Vanes L, Tybulewicz V, Di Santo J . Dissecting NK cell development using a novel alymphoid mouse model: investigating the role of the c-abl proto-oncogene in murine NK cell differentiation. J Immunol. 1999; 162(5):2761-5. View