Dendritic Cell Depletion In Vivo

1. Introduction

Dendritic cells (DCs) are crucial immune system components, acting as primary antigen-presenting cells that bridge the innate and adaptive immune responses [1]. Depleting dendritic cells in vivo is a standard experimental technique to study their functions and the subsequent effects on immune responses [2]. 

2. What is Dendritic Cell Depletion? 

Dendritic cell depletion refers to the targeted reduction or elimination of dendritic cells in a living organism. This is typically achieved through various methods such as genetic manipulation, pharmacological agents, or specific antibodies targeting dendritic cell surface markers [3, 4]. 

3. Why Deplete Dendritic Cells In Vivo?

Researchers may wish to deplete dendritic cells in vivo for several reasons:

Studying Immune Responses: Understanding the role of dendritic cells in initiating and regulating immune responses, including autoimmunity, infection, and cancer.
Investigating Disease Mechanisms: Examining how the absence of dendritic cells affects disease progression, such as in autoimmune diseases, infectious diseases, and tumors.
Therapeutic Development: Assessing the potential of dendritic cell depletion as a therapeutic strategy in conditions like transplant rejection and autoimmune diseases.

4. Antibody Clones Commonly Used for Dendritic Cell Depletion In Vivo

Antibodies targeting specific surface markers on dendritic cells are commonly used for their depletion in vivo. These include:

N418 (anti-CD11c): A widely used antibody clone targeting dendritic cells in mice.

33D1 (anti-DEC205): Another commonly used antibody for mouse dendritic cells. Targets DEC205, a receptor expressed on a subset of dendritic cells, mainly in mice.

DNL-4 (anti-CD11c): Used in rats for dendritic cell targeting.

CD11c.4 (anti-CD11c): Used for targeting dendritic cells in non-human primates.

5. Focus on Antibody Clone N418

Advantages of N418:

N418 is an anti-CD11c antibody clone highly specific for dendritic cells in mice. CD11c is a component of the integrin receptor complex found predominantly on dendritic cells, making N418 an effective tool for their depletion [5]. The advantages of using N418 include:

Specificity: High specificity for CD11c+ dendritic cells, ensuring targeted depletion.
Established Protocols: Well-documented usage in numerous studies, providing a wealth of background information and established methodologies.
Availability: Commercially available and widely used, facilitating reproducibility and cross-study comparisons.

 
Pitfalls of N418:

Despite its advantages, there are some pitfalls associated with using N418:

Species Specificity: N418 is primarily effective in mice and may not be suitable for other species.

Off-Target Effects: There is potential for off-target effects, particularly in tissues where CD11c is expressed by other cell types, like macrophages.

Dosage Optimization: Requires careful dosage optimization to avoid incomplete depletion or excessive off-target effects.

6. Commonly Used Dosage of N418

The typical dosage of N418 for effective dendritic cell depletion in mice ranges from 100 µg to 200 µg per mouse, administered intraperitoneally or intravenously. Dosage may vary depending on the specific experimental design and the desired level of depletion [6]. 

7. Highly Cited Articles of Dendritic Cell Depletion 

Several articles have explained the role of dendritic cell depletion in treating different diseases and for in vivo research using the N418 antibody clone and other clones. Here are some of them.  

Wang et al. (2000) demonstrated that small amounts of protein antigen may be delivered to dendritic cells in vivo in a single step with assistance, and this can result in rapid and potent antibody responses. This strategy might benefit vaccinations given right before or after exposure to a virus [7].  

Another study by Huarte et al. (2008) reported that the depletion of dendritic cells delays ovarian cancer progression by boosting anti-tumor immunity with CD11c+DEC205+ [8]. 
According to Volckmar et al. (2010) illustrated the Chemical Conjugation of a Purified DEC-205-Directed Antibody with Full-Length Protein for Targeting Mouse Dendritic Cells in Vitro and in Vivo [9]. 

8. Conclusion

Depleting dendritic cells in vivo using antibody clones like N418 provides valuable insights into the immune system and disease mechanisms. While N418 offers high specificity and is widely used, carefully considering its dosage and potential off-target effects is crucial. Researchers can explore other antibody clones like 33D1 for different experimental needs and species. The continued study and application of these techniques will enhance our understanding of dendritic cell functions and their therapeutic potential. 

By adhering to the guidelines outlined in this guide, researchers can effectively deplete dendritic cells in vivo and contribute to the advancing field of immunology.

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                                      2. https://ichor.bio/anti-mouse-dendritic-cells-33d1-in-vivo-antibody-low-endotoxin

                                     3. https://ichor.bio/anti-cd11c-in-vivo-antibody-low-endotoxin-3-9-ich1008

9. References 

1.      Soto JA, Gálvez NMS, Andrade CA, Pacheco GA, Bohmwald K, Berrios RV, Bueno SM, Kalergis AM. The Role of Dendritic Cells During Infections Caused by Highly Prevalent Viruses. Front Immunol. 2020 Jul 16; 11:1513. 

2.      Kurilin V, Alshevskaya A, Sennikov S. Development of Cell Technologies Based on Dendritic Cells for Immunotherapy of Oncological Diseases. Biomedicines. 2024 Mar 21;12(3):699. 

3.      Zanna MY, Yasmin AR, Omar AR, Arshad SS, Mariatulqabtiah AR, Nur-Fazila SH, Mahiza MIN. Review of Dendritic Cells, Their Role in Clinical Immunology, and Distribution in Various Animal Species. Int J Mol Sci. 2021 Jul 28;22(15):8044.

4.      Fucikova J, Palova-Jelinkova L, Bartunkova J, Spisek R. Induction of Tolerance and Immunity by Dendritic Cells: Mechanisms and Clinical Applications. Front Immunol. 2019 Oct 29; 10:2393. 

5.      https://www.thermofisher.com/antibody/product/CD11c-Antibody-clone-N418-Monoclonal/14-0114-82 [Extracted information on 16 July 2024]

6.      Ho WW, Gomes-Santos IL, Aoki S, Datta M, Kawaguchi K, Talele NP, Roberge S, Ren J, Liu H, Chen IX, Andersson P, Chatterjee S, Kumar AS, Amoozgar Z, Zhang Q, Huang P, Ng MR, Chauhan VP, Xu L, Duda DG, Clark JW, Pittet MJ, Fukumura D, Jain RK. Dendritic cell paucity in mismatch repair-proficient colorectal cancer liver metastases limits immune checkpoint blockade efficacy. Proc Natl Acad Sci U S A. 2021 Nov 9;118(45): e2105323118. 

7.      Wang H, Griffiths MN, Burton DR, Ghazal P. Rapid antibody responses by low-dose, single-step, dendritic cell-targeted immunization. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):847-52. doi: 10.1073/pnas.97.2.847. PMID: 10639168; PMCID: PMC15419.

8.      Huarte E, Cubillos-Ruiz JR, Nesbeth YC, Scarlett UK, Martinez DG, Buckanovich RJ, Benencia F, Stan RV, Keler T, Sarobe P, Sentman CL, Conejo-Garcia JR. Depletion of dendritic cells delays ovarian cancer progression by boosting antitumor immunity. Cancer Res. 2008 Sep 15;68(18):7684-91. 

9.      Volckmar J, Knop L, Hirsch T, Frentzel S, Erck C, van Ham M, Stegemann-Koniszewski S, Bruder D. Chemical Conjugation of a Purified DEC-205-Directed Antibody with Full-Length Protein for Targeting Mouse Dendritic Cells In Vitro and In Vivo. J Vis Exp. 2021 Feb 5;(168).