No abstract

Lymph node (LN) stromal cell populations expand during the inflammation that accompanies T cell activation. Interleukin 17 (IL-17)-producing T helper (TH17) cells promote inflammation through induction of cytokines and chemokines in peripheral tissues. We demonstrate a critical requirement for IL-17 in the proliferation of lymph node (LN) and spleen stromal cells, particularly fibroblastic reticular cells (FRCs), during experimental autoimmune encephalomyelitis and colitis. Without IL-17 receptor signaling, activated FRCs underwent cell cycle arrest and ultimately apoptosis, accompanied by signs of nutrient stress in vivo. IL-17 signaling in FRCs was not required for TH17 cell development, but failed FRC proliferation impaired germinal center formation and antigen-specific antibody production. IL-17 induction of the transcriptional coactivator IκBζ mediated increased glucose uptake and mitochondrial Cpt1a expression. Hence, IL-17 produced by locally differentiating TH17 cells is an important driver of inflamed LN stromal cell activation, through metabolic reprogramming required to support proliferation and survival.

CD4 + T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4 + Th cells are complex and less well understood. In human autoimmune diseases such as multiple sclerosis (MS), there is a critical need to better understand the function and biology of memory T cells. In this review article we summarize current concepts in the field of CD4 + T cell memory, including natural history, developmental pathways, subsets, and functions. Furthermore, we discuss advancements in the field of the newly-described CD4 + tissue-resident memory T cells and of CD4 + memory T cells in autoimmune diseases, two major areas of important unresolved questions in need of answering to advance new vaccine design and development of novel treatments for CD4 + T cell-mediated autoimmune diseases.