BACKGROUND: The concept of the polarization of chemokine receptor expression by T(H)1 and T(H)2 cells provides an attractive mechanism for their differential recruitment to tissue, which could be subject to disease-specific therapeutic intervention. The paradigm that T(H)1 cells preferentially express CXCR 3 and CCR 5 and T(H)2 cells preferentially express CCR 3, CCR 4, and CCR 8 has been well established in the setting of in vitro polarized cell lines; however, the situation in vivo appears less clear-cut. OBJECTIVE: We sought to investigate whether this pattern of polarization can be demonstrated in human lung tissue. METHODS: We used single-cell analysis to investigate the relationship between chemokine receptor expression and cytokine production on peripheral blood and bronchoalveolar lavage fluid T cells in patients with asthma, a putative T(H)2 disease, as well as in healthy control subjects. RESULTS: We have found in both asthmatic and control subjects that IL-4-expressing blood and bronchoalveolar lavage fluid T cells are significantly more likely to express the T(H)2 type 2 chemokine receptors CCR 3 and CCR 4, with 10-fold and 2-fold differences in expression, respectively, compared with IFN-gamma-expressing cells. CONCLUSION: We have provided evidence that polarization of T(H)2-type chemokine receptors on IL-4-expressing cells can be demonstrated in an in vivo setting and therefore that these cells might indeed be susceptible to differential patterns of recruitment as a result of expression of the relevant chemokines at inflammatory sites.
BACKGROUND: The concept of the polarization of chemokine receptor expression by T(H)1 and T(H)2 cells provides an attractive mechanism for their differential recruitment to tissue, which could be subject to disease-specific therapeutic intervention. The paradigm that T(H)1 cells preferentially express CXCR 3 and CCR 5 and T(H)2 cells preferentially express CCR 3, CCR 4, and CCR 8 has been well established in the setting of in vitro polarized cell lines; however, the situation in vivo appears less clear-cut. OBJECTIVE: We sought to investigate whether this pattern of polarization can be demonstrated in human lung tissue. METHODS: We used single-cell analysis to investigate the relationship between chemokine receptor expression and cytokine production on peripheral blood and bronchoalveolar lavage fluid T cells in patients with asthma, a putative T(H)2 disease, as well as in healthy control subjects. RESULTS: We have found in both asthmatic and control subjects that IL-4-expressing blood and bronchoalveolar lavage fluid T cells are significantly more likely to express the T(H)2 type 2 chemokine receptors CCR 3 and CCR 4, with 10-fold and 2-fold differences in expression, respectively, compared with IFN-gamma-expressing cells. CONCLUSION: We have provided evidence that polarization of T(H)2-type chemokine receptors on IL-4-expressing cells can be demonstrated in an in vivo setting and therefore that these cells might indeed be susceptible to differential patterns of recruitment as a result of expression of the relevant chemokines at inflammatory sites.
Authors: E Danilova; I Skrindo; E Gran; B J Hales; W A Smith; J Jahnsen; F E Johansen; F L Jahnsen; E S Baekkevold Journal: Mucosal Immunol Date: 2014-06-11 Impact factor: 7.313
Authors: Mike Berry; Angela Morgan; Dominick E Shaw; Deborah Parker; Ruth Green; Christopher Brightling; Peter Bradding; Andrew J Wardlaw; Ian D Pavord Journal: Thorax Date: 2007-03-13 Impact factor: 9.139
Authors: K Mutalithas; C Guillen; C Raport; R Kolbeck; D Soler; C E Brightling; I D Pavord; A J Wardlaw Journal: Clin Exp Allergy Date: 2010-04-28 Impact factor: 5.018
Authors: R Saunders; A Sutcliffe; L Woodman; D Kaur; S Siddiqui; Y Okayama; A Wardlaw; P Bradding; C Brightling Journal: Allergy Date: 2008-09 Impact factor: 13.146