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. 1997 May;91(1):145–150. doi: 10.1046/j.1365-2567.1997.00321.x

Steroids inhibit uptake and/or processing but not presentation of antigen by airway dendritic cells.

P G Holt 1, J A Thomas 1
PMCID: PMC1364047  PMID: 9203978

Abstract

Recent studies from our laboratory indicate that local and (particularly) systemic steroids can modulate the traffic of dendritic cells (DC) through resting and inflamed airway epithelial tissues. The present report focuses upon the T-cell activating properties of DC, which are controlled by granulocyte-macrophage colony-stimulating factor (GM-CSF) signals, and in particular the question of whether the DC-stimulating effects of GM-CSF are susceptible to regulation by steroids. We present evidence that while dexamethasone inhibited GM-CSF-dependent uptake and/or processing of exogenous antigen by DC, it was ineffective in blocking the presentation of preprocessed self antigen to alloreactive T cells in a one-way mixed lymphocyte reaction (MLR). Associated GM-CSF-induced up-regulation of major histocompatability complex (MHC) class II and CTLA4 ligand expression by DC were also unaffected by dexamethasone phosphate (DX), reinforcing the view that the inhibitory effects of steroids on the T-cell activating functions of DC are restricted to steps upstream from presentation of processed antigen to the T-cell receptor (TCR). These findings have potentially important implications in relation to the use of topical steroids in the treatment of atopic asthma, a disease in which local T-cell activation in airway tissue is a key pathogenic factor, and which furthermore is characterized by intense production of GM-CSF within the airway epithelium.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armstrong L. R., Christensen P. J., Paine R., 3rd, Chen G. H., McDonald R. A., Lim T. K., Toews G. B. Regulation of the immunostimulatory activity of rat pulmonary interstitial dendritic cells by cell-cell interactions and cytokines. Am J Respir Cell Mol Biol. 1994 Dec;11(6):682–691. doi: 10.1165/ajrcmb.11.6.7946397. [DOI] [PubMed] [Google Scholar]
  2. Berman B., France D. S., Martinelli G. P., Hass A. Modulation of expression of epidermal Langerhans cell properties following in situ exposure to glucocorticosteroids. J Invest Dermatol. 1983 Mar;80(3):168–171. doi: 10.1111/1523-1747.ep12533397. [DOI] [PubMed] [Google Scholar]
  3. Corrigan C. J., Kay A. B. T cells and eosinophils in the pathogenesis of asthma. Immunol Today. 1992 Dec;13(12):501–507. doi: 10.1016/0167-5699(92)90026-4. [DOI] [PubMed] [Google Scholar]
  4. Eckels D. D. Alloreactivity: allogeneic presentation of endogenous peptide or direct recognition of MHC polymorphism? A review. Tissue Antigens. 1990 Feb;35(2):49–55. doi: 10.1111/j.1399-0039.1990.tb01755.x. [DOI] [PubMed] [Google Scholar]
  5. Fisch A., Reske K. Cell surface display of rat invariant gamma chain: detection by monoclonal antibodies directed against a C-terminal gamma chain segment. Eur J Immunol. 1992 Jun;22(6):1413–1419. doi: 10.1002/eji.1830220613. [DOI] [PubMed] [Google Scholar]
  6. Holt P. G., Haining S., Nelson D. J., Sedgwick J. D. Origin and steady-state turnover of class II MHC-bearing dendritic cells in the epithelium of the conducting airways. J Immunol. 1994 Jul 1;153(1):256–261. [PubMed] [Google Scholar]
  7. Holt P. G. Macrophage: dendritic cell interaction in regulation of the IgE response in asthma. Clin Exp Allergy. 1993 Jan;23(1):4–6. doi: 10.1111/j.1365-2222.1993.tb02476.x. [DOI] [PubMed] [Google Scholar]
  8. Holt P. G., Oliver J., Bilyk N., McMenamin C., McMenamin P. G., Kraal G., Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med. 1993 Feb 1;177(2):397–407. doi: 10.1084/jem.177.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holt P. G. Regulation of antigen-presenting cell function(s) in lung and airway tissues. Eur Respir J. 1993 Jan;6(1):120–129. [PubMed] [Google Scholar]
  10. Holt P. G., Schon-Hegrad M. A., Oliver J., Holt B. J., McMenamin P. G. A contiguous network of dendritic antigen-presenting cells within the respiratory epithelium. Int Arch Allergy Appl Immunol. 1990;91(2):155–159. doi: 10.1159/000235107. [DOI] [PubMed] [Google Scholar]
  11. Holt P. G., Schon-Hegrad M. A., Oliver J. MHC class II antigen-bearing dendritic cells in pulmonary tissues of the rat. Regulation of antigen presentation activity by endogenous macrophage populations. J Exp Med. 1988 Feb 1;167(2):262–274. doi: 10.1084/jem.167.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holt P. G., Schon-Hegrad M. A., Phillips M. J., McMenamin P. G. Ia-positive dendritic cells form a tightly meshed network within the human airway epithelium. Clin Exp Allergy. 1989 Nov;19(6):597–601. doi: 10.1111/j.1365-2222.1989.tb02752.x. [DOI] [PubMed] [Google Scholar]
  13. Linsley P. S., Brady W., Urnes M., Grosmaire L. S., Damle N. K., Ledbetter J. A. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991 Sep 1;174(3):561–569. doi: 10.1084/jem.174.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McWilliam A. S., Nelson D., Thomas J. A., Holt P. G. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J Exp Med. 1994 Apr 1;179(4):1331–1336. doi: 10.1084/jem.179.4.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moser M., De Smedt T., Sornasse T., Tielemans F., Chentoufi A. A., Muraille E., Van Mechelen M., Urbain J., Leo O. Glucocorticoids down-regulate dendritic cell function in vitro and in vivo. Eur J Immunol. 1995 Oct;25(10):2818–2824. doi: 10.1002/eji.1830251016. [DOI] [PubMed] [Google Scholar]
  16. Möller G. M., Overbeek S. E., Van Helden-Meeuwsen C. G., Van Haarst J. M., Prens E. P., Mulder P. G., Postma D. S., Hoogsteden H. C. Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clin Exp Allergy. 1996 May;26(5):517–524. [PubMed] [Google Scholar]
  17. Nelson D. J., McWilliam A. S., Haining S., Holt P. G. Modulation of airway intraepithelial dendritic cells following exposure to steroids. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):475–481. doi: 10.1164/ajrccm.151.2.7842209. [DOI] [PubMed] [Google Scholar]
  18. Poston R. N., Chanez P., Lacoste J. Y., Litchfield T., Lee T. H., Bousquet J. Immunohistochemical characterization of the cellular infiltration in asthmatic bronchi. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):918–921. doi: 10.1164/ajrccm/145.4_Pt_1.918. [DOI] [PubMed] [Google Scholar]
  19. Schon-Hegrad M. A., Oliver J., McMenamin P. G., Holt P. G. Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (Ia)-bearing dendritic cells (DC) in the conducting airways. J Exp Med. 1991 Jun 1;173(6):1345–1356. doi: 10.1084/jem.173.6.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Semper A. E., Hartley J. A. Dendritic cells in the lung: what is their relevance to asthma? Clin Exp Allergy. 1996 May;26(5):485–490. [PubMed] [Google Scholar]
  21. Sertl K., Takemura T., Tschachler E., Ferrans V. J., Kaliner M. A., Shevach E. M. Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura. J Exp Med. 1986 Feb 1;163(2):436–451. doi: 10.1084/jem.163.2.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Soler P., Moreau A., Basset F., Hance A. J. Cigarette smoking-induced changes in the number and differentiated state of pulmonary dendritic cells/Langerhans cells. Am Rev Respir Dis. 1989 May;139(5):1112–1117. doi: 10.1164/ajrccm/139.5.1112. [DOI] [PubMed] [Google Scholar]
  23. Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]

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