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...

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Auteurs principaux:	Fabio Morandi, Elisa Ferretti, Paola Bocca, Ignazia Prigione, Lizzia Raffaghello, Vito Pistoia
Format:	article
Langue:	EN
Publié:	Public Library of Science (PLoS) 2010
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/45c76a94729640a99fddb6e4f1e26e2c
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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
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A novel mechanism of soluble HLA-G mediated immune modulation: downregulation of T cell chemokine receptor expression and impairment of chemotaxis.

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