Jan 31, 2018

Distinctive expression of T cell guiding molecules in human autoimmune lymph node stromal cells upon TLR3 triggering

Scientific Reports
Janine HähnleinLisa G M van Baarsen

Abstract

Infections are implicated in autoimmunity. Autoantibodies are produced in lymphoid tissue where lymph node stromal cells (LNSCs) regulate lymphocyte function. Infections can alter the interaction between LNSCs and lymphocytes resulting in defective immune responses. In rheumatoid arthritis (RA) autoantibody production precedes clinical disease allowing identification of at risk individuals. We investigated the ability of human LNSCs derived from RA, RA-risk and healthy individuals to sense and respond to pathogens. Human LNSCs cultured directly from freshly collected lymph node biopsies expressed TLR1-9 with exception of TLR7. In all donors TLR3 triggering induced expression of ISGs, IL-6 and adhesion molecules like VCAM-1 and ICAM-1. Strikingly, T cell guiding chemokines CCL19 and IL-8 as well as the antiviral gene MxA were less induced upon TLR3 triggering in autoimmune LNSCs. This observed decrease, found already in LNSCs of RA-risk individuals, may lead to incorrect positioning of lymphocytes and aberrant immune responses during viral infections.

  • References70
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References

  • References70
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Citations

Mentioned in this Paper

TLR3 protein, human
Immune Response
Autoantibodies
T-Lymphocyte
TLR7 protein, human
MX1
Virus Diseases
Lymphocytes as Percentage of Blood Leukocytes (Lab Test)
CCL19
Intercellular adhesion molecule 1

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