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Chemokines and common variable immunodeficiency; possible contribution of CCL19, CCL21 and CCR7 to immune dysregulation.

Abstract：

:Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. The homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 are associated with modulation of inflammatory responses. CVID patients have decreased proportions of CCR7(+) T cells in peripheral blood and we hypothesized a further dysregulation of CCL19/CCL21/CCR7 in CVID. Serum levels of CCL19 and CCL21 were compared in CVID patients and controls. T cell expression of CCR7 was related to clinical characteristics in CVID patients. Spleens extirpated from CVID patients were analysed for expression of CCL19, CCL21 and CCR7. Peripheral blood mononuclear cells (PBMC) from CVID patients and controls were analysed for cytokine response on stimulation with CCL19 and CCL21. The main findings were: (i) CVID patients have raised serum levels of CCL19 and CCL21 independently of features of chronic inflammation; (ii) CCL19 and CCR7 have similar expression in spleens from CVID patients and controls, while CCL21 is variably down-regulated in spleens from patients; (iii) T cell expression of CCR7 is particularly low in patients characterized by chronic inflammation in vivo; and (iv) PBMC from CVID patients had attenuated cytokine response to stimulation with CCL19 and CCL21. CVID patients have raised circulatory levels of CCL19 and CCL21, and an attenuated cytokine response to stimulation with these chemokines. Because CCR7, CCL19 and CCL21 are key mediators balancing immunity and tolerance in the immune system, the abnormalities of these mediators might contribute to the profound immune dysregulation seen in CVID.

journal_name

Clin Exp Immunol

journal_title

Clinical and experimental immunology

authors

Fevang B,Yndestad A,Damås JK,Halvorsen B,Holm AM,Beiske K,Aukrust P,Frøland SS

doi

10.1111/j.1365-2249.2009.04013.x

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

237-45

issue

eissn

0009-9104

issn

1365-2249

pii

CEI4013

journal_volume

158

pub_type

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Chemokines and common variable immunodeficiency; possible contribution of CCL19, CCL21 and CCR7 to immune dysregulation.