Targeting fibroblastic reticular cells to modulate the immune response in the lymph node

Abstract

Lymph nodes, in which foreign antigens are presented with the help of antigen-presenting cells to naive lymphocytes, are important for the initiation of an immune response. Fibroblastic reticular cells (FRC) produce the extracellular matrix that forms the reticular conduit system, which provides structural support to the lymph node and sorts the soluble antigens based on their size into the lymph node parenchyma. During inflammation, the lymph node stroma is remodeled through stretching of the conduit system and proliferation of the FRCs to support the growing lymphocyte population. This thesis established a local FRC depletion model in the lymph nodes of CCL19-Cre x iDTR (CCL19-iDTR) mice and investigated the response of the lymph nodes with reduced FRC population during inflammation. Our results indicate that the expression of Cre or Cre-inducible diphtheria toxin receptor (iDTR) does not affect the FRC number, and the CCL19-iDTR mouse model has the same initial amount of FRCs as wild-type mice. An injection of diphtheria toxin can reduce the FRC population by half in the draining popliteal lymph node in the CCL19- iDTR mouse model, but the depletion does not remain local. The draining popliteal lymph node can also respond to immunization after FRC depletion, but the expansion is not as effective as during normal circumstances. In conclusion, the FRCs regulate the immune response in the lymph node, but further studies are needed to determine their exact role during inflammation.