A novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis.
<h4>Background</h4>In recent years, many immunoregulatory functions have been ascribed to soluble HLA-G (sHLA-G). Since chemotaxis is crucial for an efficient immune response, we have investigated for the first time the effects of sHLA-G on chemokine receptor expression and function in d...
Guardado en:
| Autores principales: | , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2010
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/45c76a94729640a99fddb6e4f1e26e2c |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:45c76a94729640a99fddb6e4f1e26e2c |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:45c76a94729640a99fddb6e4f1e26e2c2021-12-02T20:19:47ZA novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis.1932-620310.1371/journal.pone.0011763https://doaj.org/article/45c76a94729640a99fddb6e4f1e26e2c2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20668702/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>In recent years, many immunoregulatory functions have been ascribed to soluble HLA-G (sHLA-G). Since chemotaxis is crucial for an efficient immune response, we have investigated for the first time the effects of sHLA-G on chemokine receptor expression and function in different human T cell populations.<h4>Methodology/principal findings</h4>T cell populations isolated from peripheral blood were stimulated in the presence or absence of sHLA-G. Chemokine receptors expression was evaluated by flow cytometry. sHLA-G downregulated expression of i) CCR2, CXCR3 and CXCR5 in CD4(+) T cells, ii) CXCR3 in CD8(+) T cells, iii) CXCR3 in Th1 clones iv) CXCR3 in TCR Vdelta2gamma9 T cells, and upregulated CXCR4 expression in TCR Vdelta2gamma9 T cells. sHLA-G inhibited in vitro chemotaxis of i) CD4(+) T cells towards CCL2, CCL8, CXCL10 and CXCL11, ii) CD8(+) T cells towards CXCL10 and CXCL11, iii) Th1 clones towards CXCL10, and iv) TCR Vdelta2gamma9 T cells towards CXCL10 and CXCL11. Downregulation of CXCR3 expression on CD4+ T cells by sHLA-G was partially reverted by adding a blocking antibody against ILT2/CD85j, a receptor for sHLA-G, suggesting that sHLA-G downregulated chemokine receptor expression mainly through the interaction with ILT2/CD85j. Follicular helper T cells (T(FH)) were isolated from human tonsils and stimulated as described above. sHLA-G impaired CXCR5 expression in T(FH) and chemotaxis of the latter cells towards CXCL13. Moreover, sHLA-G expression was detected in tonsils by immunohistochemistry, suggesting a role of sHLA-G in local control of T(FH) cell chemotaxis. Intracellular pathways were investigated by Western Blot analysis on total extracts from CD4+ T cells. Phosphorylation of Stat5, p70 s6k, beta-arrestin and SHP2 was modulated by sHLA-G treatment.<h4>Conclusions/significance</h4>Our data demonstrated that sHLA-G impairs expression and functionality of different chemokine receptors in T cells. These findings delineate a novel mechanism whereby sHLA-G modulates T cell recruitment in physiological and pathological conditions.Fabio MorandiElisa FerrettiPaola BoccaIgnazia PrigioneLizzia RaffaghelloVito PistoiaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11763 (2010) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Fabio Morandi Elisa Ferretti Paola Bocca Ignazia Prigione Lizzia Raffaghello Vito Pistoia A novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis. |
| description |
<h4>Background</h4>In recent years, many immunoregulatory functions have been ascribed to soluble HLA-G (sHLA-G). Since chemotaxis is crucial for an efficient immune response, we have investigated for the first time the effects of sHLA-G on chemokine receptor expression and function in different human T cell populations.<h4>Methodology/principal findings</h4>T cell populations isolated from peripheral blood were stimulated in the presence or absence of sHLA-G. Chemokine receptors expression was evaluated by flow cytometry. sHLA-G downregulated expression of i) CCR2, CXCR3 and CXCR5 in CD4(+) T cells, ii) CXCR3 in CD8(+) T cells, iii) CXCR3 in Th1 clones iv) CXCR3 in TCR Vdelta2gamma9 T cells, and upregulated CXCR4 expression in TCR Vdelta2gamma9 T cells. sHLA-G inhibited in vitro chemotaxis of i) CD4(+) T cells towards CCL2, CCL8, CXCL10 and CXCL11, ii) CD8(+) T cells towards CXCL10 and CXCL11, iii) Th1 clones towards CXCL10, and iv) TCR Vdelta2gamma9 T cells towards CXCL10 and CXCL11. Downregulation of CXCR3 expression on CD4+ T cells by sHLA-G was partially reverted by adding a blocking antibody against ILT2/CD85j, a receptor for sHLA-G, suggesting that sHLA-G downregulated chemokine receptor expression mainly through the interaction with ILT2/CD85j. Follicular helper T cells (T(FH)) were isolated from human tonsils and stimulated as described above. sHLA-G impaired CXCR5 expression in T(FH) and chemotaxis of the latter cells towards CXCL13. Moreover, sHLA-G expression was detected in tonsils by immunohistochemistry, suggesting a role of sHLA-G in local control of T(FH) cell chemotaxis. Intracellular pathways were investigated by Western Blot analysis on total extracts from CD4+ T cells. Phosphorylation of Stat5, p70 s6k, beta-arrestin and SHP2 was modulated by sHLA-G treatment.<h4>Conclusions/significance</h4>Our data demonstrated that sHLA-G impairs expression and functionality of different chemokine receptors in T cells. These findings delineate a novel mechanism whereby sHLA-G modulates T cell recruitment in physiological and pathological conditions. |
| format |
article |
| author |
Fabio Morandi Elisa Ferretti Paola Bocca Ignazia Prigione Lizzia Raffaghello Vito Pistoia |
| author_facet |
Fabio Morandi Elisa Ferretti Paola Bocca Ignazia Prigione Lizzia Raffaghello Vito Pistoia |
| author_sort |
Fabio Morandi |
| title |
A novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis. |
| title_short |
A novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis. |
| title_full |
A novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis. |
| title_fullStr |
A novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis. |
| title_full_unstemmed |
A novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis. |
| title_sort |
novel mechanism of soluble hla-g mediated immune modulation: downregulation of t cell chemokine receptor expression and impairment of chemotaxis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/45c76a94729640a99fddb6e4f1e26e2c |
| work_keys_str_mv |
AT fabiomorandi anovelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT elisaferretti anovelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT paolabocca anovelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT ignaziaprigione anovelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT lizziaraffaghello anovelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT vitopistoia anovelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT fabiomorandi novelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT elisaferretti novelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT paolabocca novelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT ignaziaprigione novelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT lizziaraffaghello novelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis AT vitopistoia novelmechanismofsolublehlagmediatedimmunemodulationdownregulationoftcellchemokinereceptorexpressionandimpairmentofchemotaxis |
| _version_ |
1718374162503827456 |