Macrophages drive inguinal fat pad and lymph node remodelling in response to peripheral inflammation.

Adaptive immune responses are intensely energy-dependent and rely on a local source of fuel-producing molecules which have been proposed to be derived from fat pads in which mammalian lymph nodes are embedded. However, the trigger for their release has not been identified. Here we demonstrate that cutaneous inflammation is directly correlated with rapid atrophy of perinodal fat pads and increase in embedded lymph node size. We further demonstrate that the fat pad atrophy is associated with influx of a CCR2-independent, lipid metabolising, macrophage population. Macrophage depletion ameliorates fat pad atrophy, and lymph node expansion, downstream of inflamed sites. Our data therefore identify peripheral inflammation as an antigen-independent trigger of downstream fat pad and lymph node remodelling and contributes to the release of essential nutrients to drive the energetic requirements of the adaptive immune response. Significance statementTo our knowledge, this striking correlation between peripheral inflammation and reciprocal fat pad and lymph node remodelling has not been reported previously. Our report of this correlation and our mechanistic insight, have clear implications for our understanding of the inflammation-driven rapid release of sources of energy from fat pads to drive the immune response. Our data also potentially shed light on additional aspects of the functionality of pro-inflammatory vaccine adjuvants. We believe that our findings are fully novel and will be of interest to immunologists, infectious disease specialists and researchers interested in adipose tissue derived energetics.