Skip to main content
SpringerLink
Log in

Macrophage Subset Expressing CD169 in Peritoneal Cavity-Regulated Mucosal Inflammation Together with Lower Levels of CCL22

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of inflammatory bowel diseases (IBD) and have been paid more attention due to their increasing incidence and a substantial increase in the risk of colorectal cancer (CRC). However, the phenotype and, more importantly, the function in the regulation of mucosal inflammation by different macrophages are poorly understood, even though macrophages constitute a major subset of intestinal myeloid cells. The results firstly showed that the subset of peritoneal CD11b+CD169+ macrophages increased and CCL22 expression level decreased significantly during the DSS-induced colitis. DSS-induced colitis was alleviated in CD169-DTR mice at least partially due to the deletion CD169+ macrophages. Moreover, the CCL22 expression level in peritoneal macrophages from CD169-DTR mice was much higher than that from WT mice with DSS-induced colitis. And, the cell-sorting result revealed that CD11b+CD169+ macrophage cells did not express CCL22 dominantly. Further experiment in vivo demonstrated that treatment with recombinant murine CCL22 (rmCCL22) ameliorated the clinical symptoms of DSS-induced colitis. All these data indicated that macrophage subset of CD11b+CD169+ from peritoneal cavity played critical role probably together with low levels of CCL22 in DSS-induced colitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Abbreviations

CD169:

Cluster of differentiation 169

CCL22:

C-C motif chemokine 22

DSS:

Dextran sulfate sodium

DT:

Diphtheria toxin

DTR:

Diphtheria toxin receptor

Tregs:

Regulatory T cells

UC:

Ulcerative colitis

IBD:

Inflammatory bowel diseases.

Reference

  1. Kilcoyne, A., J.L. Kaplan, and M.S. Gee. 2016. Inflammatory bowel disease imaging: Current practice and future directions. World Journal of Gastroenterology 22: 917–932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kaistha, A., and J. Levine. 2014. Inflammatory bowel disease: The classic gastrointestinal autoimmune disease. Current Problems in Pediatric and Adolescent Health Care 44: 328–334.

    Article  PubMed  Google Scholar 

  3. Itzkowitz, S.H., and X. Yio. 2004. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: The role of inflammation. American Journal of Physiology: Gastrointestinal and Liver Physiology 287: G7–17.

    CAS  PubMed  Google Scholar 

  4. de Souza, H.S., and C. Fiocchi. 2016. Immunopathogenesis of IBD: Current state of the art. Nature Reviews. Gastroenterology & Hepatology 13: 13–27.

    Article  Google Scholar 

  5. Davies, L.C., S.J. Jenkins, J.E. Allen, and P.R. Taylor. 2013. Tissue-resident macrophages. Nature Immunology 14: 986–995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gross, M., T.M. Salame, and S. Jung. 2015. Guardians of the Gut-Murine Intestinal Macrophages and Dendritic Cells. Frontiers in Immunology 6: 254.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Yona, S., K.W. Kim, Y. Wolf, A. Mildner, D. Varol, M. Breker, et al. 2013. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38: 79–91.

    Article  CAS  PubMed  Google Scholar 

  8. Asano, K., N. Takahashi, M. Ushiki, M. Monya, F. Aihara, E. Kuboki, et al. 2015. Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes. Nature Communications 6: 7802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Martinez-Pomares, L., and S. Gordon. 2012. CD169+ macrophages at the crossroads of antigen presentation. Trends in Immunology 33: 66–70.

    Article  CAS  PubMed  Google Scholar 

  10. Asano, K., A. Nabeyama, Y. Miyake, C.H. Qiu, A. Kurita, M. Tomura, et al. 2011. CD169-positive macrophages dominate antitumor immunity by cross presenting dead cell-associated antigens. Immunity 34: 85–95.

    Article  CAS  PubMed  Google Scholar 

  11. Ravishankar, B., R. Shinde, H. Liu, K. Chaudhary, J. Bradley, H.P. Lemos, et al. 2014. Marginal zone CD169+ macrophages coordinate apoptotic cell-driven cellular recruitment and tolerance. Proceedings of the National Academy of Sciences of the United States of America 111: 4215–4220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hiemstra, I.H., M.R. Beijer, H. Veninga, K. Vrijland, E.G. Borg, B.J. Olivier, et al. 2014. The identification and development requirements of colonic CD169+ macrophages. Immunology: 142, 269–278.

  13. Cassado Ados, A., M.R. D'Império Lima, and K.R. Bortoluci. 2015. Revisiting mouse peritoneal macrophages: heterogeneity, development, and function. Frontiers in Immunology 6: 225.

    PubMed  Google Scholar 

  14. Geremia, A., P. Biancheri, P. Allan, G.R. Corazza, and A. Di Sabatino. 2014. Innate and adaptive immunity in inflammatory bowel disease. Autoimmunity Reviews 13: 3–10.

    Article  CAS  PubMed  Google Scholar 

  15. Wang, D., R.N. Dubois, and A. Richmond. 2009. The role of chemokines in intestinal inflammation and cancer. Current Opinion in Pharmacology 9: 688–696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang, J., J. Romero, A. Chan, J. Goss, S. Stucka, J. Cross, et al. 2015. Biarylsulfonamide CCR9 inhibitors for inflammatory bowel disease. Bioorganic & Medicinal Chemistry Letters 25: 3361–3364.

    Google Scholar 

  17. Evans-Marin, H.L., A.T. Cao, S. Yao, F. Chen, C. He, H. Liu, et al. 2015. Unexpected Regulatory Role of CCR9 in Regulatory T Cell Development. PloS One 10: e0134100.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Saito, Michiko, l Takao Iwawaki, Choji Taya, Hiromichi Yonekawa, Munehiro Noda, et al. Diphtheria toxin receptor–mediated conditional and targeted cell ablation in transgenic mice. Nature Biotechnology 19: 746–750.

  19. Miyake, Y. l, K. Asano, H. Kaise, M. Uemura, M. Nakayama, and M. Tanaka. Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell-associated antigens. The Journal of Clinical Investigation 117: 2268–2278.

  20. Saito, M., T. Iwawaki, C. Taya, H. Yonekawa, M. Noda, Y. Inui, et al. 2001. Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nature Biotechnology 19: 746–750.

    Article  CAS  PubMed  Google Scholar 

  21. Herwald, H., and A. Egesten. 2013. Macrophages: past, present and future. Journal of Innate Immunity 5: 657–658.

    Article  PubMed  Google Scholar 

  22. Wynn, T.A., A. Chawla, and J.W. Pollard. 2013. Macrophage biology in development, homeostasis and disease. Nature 496: 445–455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ghosn, E.E., A.A. Cassado, G.R. Govoni, T. Fukuhara, Y. Yang, D.M. Monack, et al. 2010. Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proc Natl Acad Sci U S A107: 2568–2573.

    Article  Google Scholar 

  24. Davies, L.C., M. Rosas, P.J. Smith, D.J. Fraser, S.A. Jones, and P.R. Taylor. 2011. A quantifiable proliferative burst of tissue macrophages restores homeostatic macrophage populations after acute inflammation. European Journal of Immunology 41: 2155–2164.

    Article  CAS  PubMed  Google Scholar 

  25. Davies, L.C., M. Rosas, S.J. Jenkins, C.T. Liao, M.J. Scurr, F. Brombacher, et al. 2013. Distinct bone marrow-derived and tissue-resident macrophage lineages proliferate at key stages during inflammation. Nature Communications 4: 1886.

    Article  PubMed  Google Scholar 

  26. Okabe, Y., and R. Medzhitov. 2014. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 157: 832–844.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Dahdah, A., G. Gautier, T. Attout, F. Fiore, E. Lebourdais, R. Msallam, et al. 2014. Mastcells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis. The Journal of Clinical Investigation 124: 4577–4589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Saunderson, S.C., A.C. Dunn, P.R. Crocker, and A.D. McLellan. 2014. CD169 mediates the capture of exosomes in spleen and lymph node. Blood 123: 208–216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chávez-Galán, L., M.L. Olleros, D. Vesin, and I. Garcia. 2015. Much More than M1 and M2 Macrophages, There are also CD169+ and TCR+ Macrophages. Frontiers in Immunology 6: 263.

    PubMed  PubMed Central  Google Scholar 

  30. Ohnishi, K., M. Yamaguchi, C. Erdenebaatar, F. Saito, H. Tashiro, H. Katabuchi, et al. 2016. Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma. Cancer Science 107: 846–852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li, C., X. Luo, Y. Lin, X. Tang, L. Ling, L. Wang, et al. 2015. A Higher Frequency of CD14+ CD169+ Monocytes/Macrophages in Patients with Colorectal Cancer. PloS One 10: e0141817.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Saito, Y., K. Ohnishi, A. Miyashita, S. Nakahara, Y. Fujiwara, H. Horlad, et al. 2015. Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma. Cancer Immunology Research 3: 1356–1363.

    Article  CAS  PubMed  Google Scholar 

  33. Kim, T.W., J.N. Seo, Y.H. Suh, H.J. Park, J.H. Kim, J.Y. Kim, et al. 2006. Involvement of lymphocytes in dextran sulfate sodium-induced experimental colitis. World Journal of Gastroenterology 12: 302–305.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tlaskalová-Hogenová, H., L. Tucková, R. Stepánková, T. Hudcovic, L. Palová-Jelínková, H. Kozáková, et al. 2005. Involvement of innate immunity in the development of inflammatory and autoimmune diseases. Annals of the New York Academy of Sciences 1051: 787–798.

    Article  PubMed  Google Scholar 

  35. Hartnell, A., J. Steel, H. Turley, M. Jones, D.G. Jackson, and P.R. Crocker. 2001. Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations. Blood 97 (1): 288–296.

    Article  CAS  PubMed  Google Scholar 

  36. Yoshie, O., and K. Matsushima. 2015. CCR4 and its ligands: from bench to bedside. International Immunology 27: 11–20.

    Article  CAS  PubMed  Google Scholar 

  37. Hao, S., X. Han, D. Wang, Y. Yang, Q. Li, X. Li, et al. 2016. Critical role of CCL22/CCR4 axis in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8a+CD103+ DCs. Immunology 148: 174–186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Owaga, E., R.H. Hsieh, B. Mugendi, S. Masuku, C.K. Shih, and J.S. Chang. 2015. Th17 Cells as Potential Probiotic Therapeutic Targets in Inflammatory Bowel Diseases. International Journal of Molecular Sciences 16: 20841–20858.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gálvez, J. 2014. Role of Th17 Cells in the Pathogenesis of Human IBD. ISRN Inflamm 2014: 928461.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sartor, R.B. 2006. Mechanisms of disease: Pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepato 3: 390–407.

    Article  CAS  Google Scholar 

  41. Zhang, Z., M. Zheng, J. Bindas, P. Schwarzenberger, and J.K. Kolls. 2006. Critical role of IL-17 receptor signaling in acute TNBS-induced colitis. Inflammatory Bowel Diseases 12: 382–388.

    Article  PubMed  Google Scholar 

  42. Monteleone, Ivan, Francesco Pallone, and Giovanni Monteleone. 2011. Th17-related cytokines: new players in the control of chronic intestinal inflammation. BMC Medicine 9: 122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sanchez-Munoz, F., A. Dominguez-Lopez, and J.K. Yamamoto-Furusho. 2008. Role of cytokines in inflammatory bowel disease. World Journal of Gastroenterology 14: 4280–4288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The present work was supported by grants from the (NSFC), (No. 81202306), China Postdoctoral Science Foundation (201252M1343, 2013T60674). We would like to thank Dr. Yunxue Zhao and Ms. Limei Wang at Shandong University for FACS analysis. Qiu C. and Wang D. designed the study. Wang D., Li Q., Yang Y., Hao S., Han X., Song J., and Yin Y. performed experiments. Wang D., Li X, and Qiu C. analyzed the data. Qiu C. and Wang D. wrote the paper.

Author information

Authors and Affiliations

  1. Department of Cell biology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, 250012, Shandong, People’s Republic of China

    Dan Wang, Qiuting Li, Yang Yang, Shengyu Hao, Xiaolei Han, Jia Song, Yue Yin, Xiangzhi Li & Chun-Hong Qiu

  2. Laboratory of Immune regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Masato Tanaka

Authors
  1. Dan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiuting Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yang Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shengyu Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiaolei Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jia Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yue Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiangzhi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masato Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chun-Hong Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chun-Hong Qiu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest

Electronic supplementary material

ESM 1

(PPTX 266 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, D., Li, Q., Yang, Y. et al. Macrophage Subset Expressing CD169 in Peritoneal Cavity-Regulated Mucosal Inflammation Together with Lower Levels of CCL22. Inflammation 40, 1191–1203 (2017). https://doi.org/10.1007/s10753-017-0562-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-017-0562-0

Key Words

Search

Navigation