Brief communication: Long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells

Autoři: Qingtai Su aff001;  Aurélie Bouteau aff001;  Jacob Cardenas aff003;  Balaji Uthra aff003;  Yuanyaun Wang aff003;  Cynthia Smitherman aff003;  Jinghua Gu aff003;  Botond Z. Igyártó aff001
Působiště autorů: Baylor Scott & White Research Institute, Baylor Institute for Immunology Research, Dallas, Texas, United States of America aff001;  Baylor University, Institute of Biomedical Studies, Waco, Texas, United States of America aff002;  Baylor Scott & White Research Institute, Dallas, Texas, United States of America aff003;  Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, Pennsylvania, United States of America aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223397


Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the local cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells’ biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active role in maintaining tissue homeostasis, which should be taken in consideration at data interpretation.

Klíčová slova:

Cytokines – Gene expression – Gene ontologies – Homeostasis – Immune cells – Principal component analysis – RNA sequencing – Sequence alignment


1. Lavin Y, Winter D, Blecher-Gonen R, David E, Keren-Shaul H, Merad M, et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell. 2014. doi: 10.1016/j.cell.2014.11.018 25480296

2. Pakalniškytė D, Schraml BU. Tissue-Specific Diversity and Functions of Conventional Dendritic Cells. Advances in Immunology. 2017. doi: 10.1016/ 28413024

3. Clayton K, Vallejo AF, Davies J, Sirvent S, Polak ME. Langerhans cells-programmed by the epidermis. Frontiers in Immunology. 2017. doi: 10.3389/fimmu.2017.01676 29238347

4. Romani N, Holzmann S, Tripp CH, Koch F, Stoitzner P. Langerhans cells—Dendritic cells of the epidermis. APMIS. 2003. doi: 10.1034/j.1600-0463.2003.11107805.x 12974775

5. Kaplan DH. Ontogeny and function of murine epidermal Langerhans cells. Nature Immunology. 2017. doi: 10.1038/ni.3815 28926543

6. Kaplan DH, Jenison MC, Saeland S, Shlomchik WD, Shlomchik MJ. Epidermal Langerhans cell-deficient mice develop enhanced contact hypersensitivity. Immunity. 2005. doi: 10.1016/j.immuni.2005.10.008 16356859

7. Kashem SW, Kaplan DH. Isolation of Murine Skin Resident and Migratory Dendritic Cells via Enzymatic Digestion. Curr Protoc Immunol. 2018. doi: 10.1002/cpim.45 30040218

8. Su Q, Igyártó BZ. Keratinocytes Share Gene Expression Fingerprint with Epidermal Langerhans Cells via mRNA Transfer. J Invest Dermatol. 2019. doi: 10.1016/j.jid.2019.05.006 31129057

9. Andrews S, Krueger F, Seconds-Pichon A, Biggins F, Wingett S. FastQC. A quality control tool for high throughput sequence data. Babraham Bioinformatics. Babraham Inst. 2015.

10. Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal. 2011. doi: 10.14806/ej.17.1.200

11. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009. doi: 10.1093/bioinformatics/btp352 19505943

12. Liao Y, Smyth GK, Shi W. FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics. 2014. doi: 10.1093/bioinformatics/btt656 24227677

13. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014. doi: 10.1186/s13059-014-0550-8 25516281

14. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: Tool for the unification of biology. Nature Genetics. 2000. doi: 10.1038/75556 10802651

15. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009. doi: 10.1038/nprot.2008.211 19131956

16. Sergushichev AA. An algorithm for fast preranked gene set enrichment analysis using cumulative statistic calculation. bioRxiv. 2016. doi: 10.1101/060012

17. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005. doi: 10.1073/pnas.0506580102 16199517

18. Liberzon A, Subramanian A, Pinchback R, Thorvaldsdóttir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011. doi: 10.1093/bioinformatics/btr260 21546393

19. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol. 2010. doi: 10.1186/gb-2010-11-10-r106 20979621

20. Gaujoux R, Seoighe C. A flexible R package for nonnegative matrix factorization. BMC Bioinformatics. 2010. doi: 10.1186/1471-2105-11-367 20598126

21. Ginestet C. ggplot2: Elegant Graphics for Data Analysis. J R Stat Soc Ser A (Statistics Soc. 2011. doi: 10.1111/j.1467-985x.2010.00676_9.x

22. Skaper SD. Nerve growth factor: a neuroimmune crosstalk mediator for all seasons. Immunology. 2017. doi: 10.1111/imm.12717 28112808

23. Boulais N, Misery L. The epidermis: A sensory tissue. European Journal of Dermatology. 2008. doi: 10.1684/ejd.2008.0348 18424369

24. Lee HJ, Kim TG, Kim SH, Park JY, Lee M, Lee JW, et al. Epidermal Barrier Function Is Impaired in Langerhans Cell-Depleted Mice. J Invest Dermatol. 2019. doi: 10.1016/j.jid.2018.10.036 30448384

25. Han NR, Oh HA, Nam SY, Moon PD, Kim DW, Kim HM, et al. TSLP induces mast cell development and aggravates allergic reactions through the activation of MDM2 and STAT6. J Invest Dermatol. 2014. doi: 10.1038/jid.2014.198 24751726

26. Leyva-Castillo JM, Hener P, Michea P, Karasuyama H, Chan S, Soumelis V, et al. Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade. Nat Commun. 2013. doi: 10.1038/ncomms3847 24284909

27. Nakajima S, Igyártó BZ, Honda T, Egawa G, Otsuka A, Hara-Chikuma M, et al. Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling. J Allergy Clin Immunol. 2012. doi: 10.1016/j.jaci.2012.01.063 22385635

28. Lewis JM, Bürgler CD, Freudzon M, Golubets K, Gibson JF, Filler RB, et al. Langerhans Cells Facilitate UVB-Induced Epidermal Carcinogenesis. J Invest Dermatol. 2015. doi: 10.1038/jid.2015.207 26053049

29. Modi BG, Neustadter J, Binda E, Lewis J, Filler RB, Roberts SJ, et al. Langerhans cells facilitate epithelial DNA damage and squamous cell carcinoma. Science (80-). 2012. doi: 10.1126/science.1211600 22223807

30. Cho JS, Pietras EM, Garcia NC, Ramos RI, Farzam DM, Monroe HR, et al. IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest. 2010. doi: 10.1172/JCI40891 20364087

31. Kang J, Malhotra N. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors. Annu Rev Immunol. 2015. doi: 10.1146/annurev-immunol-032414-112025 25650177

32. Taveirne S, De Colvenaer V, Van Den Broeck T, Van Ammel E, Bennett CL, Taghon T, et al. Langerhans cells are not required for epidermal V 3 T cell homeostasis and function. J Leukoc Biol. 2011. doi: 10.1189/jlb.1010581 21486908

33. Shipman WD, Chyou S, Ramanathan A, Izmirly PM, Sharma S, Pannellini T, et al. A protective Langerhans cell keratinocyte axis that is dysfunctional in photosensitivity. Sci Transl Med. 2018. doi: 10.1126/scitranslmed.aap9527 30111646

34. Bobr A, Olvera-Gomez I, Igyarto BZ, Haley KM, Hogquist KA, Kaplan DH. Acute Ablation of Langerhans Cells Enhances Skin Immune Responses. J Immunol. 2010. doi: 10.4049/jimmunol.1001802 20855870

35. Clausen BE, Stoitzner P. Functional specialization of skin dendritic cell subsets in regulating T cell responses. Front Immunol. 2015. doi: 10.3389/fimmu.2015.00534 26557117

36. Hoeffel G, Wang Y, Greter M, See P, Teo P, Malleret B, et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med. 2012. doi: 10.1084/jem.20120340 22565823

37. Obhrai JS, Oberbarnscheidt M, Zhang N, Mueller DL, Shlomchik WD, Lakkis FG, et al. Langerhans cells are not required for efficient skin graft rejection. J Invest Dermatol. 2008. doi: 10.1038/jid.2008.52 18337832

38. Igyarto BZ, Jenison MC, Dudda JC, Roers A, Müller W, Koni PA, et al. Langerhans Cells Suppress Contact Hypersensitivity Responses Via Cognate CD4 Interaction and Langerhans Cell-Derived IL-10. J Immunol. 2009. doi: 10.4049/jimmunol.0901884 19801524

39. Igyártó BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M, Edelson BT, et al. Skin-Resident Murine Dendritic Cell Subsets Promote Distinct and Opposing Antigen-Specific T Helper Cell Responses. Immunity. 2011. doi: 10.1016/j.immuni.2011.06.005 21782478

Článek vyšel v časopise


2020 Číslo 1