Analysis of transcriptomic profile of iNKT cells

The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident lymphocytes, including lipid-reactive invariant natural killer T (iNKT) cells. iNKT cells have unique properties according to their tissues of residency, but if and how the tissue environment shapes their antigen specificity remains unknown. By analysing iNKT cells from tissues of mice and humans we demonstrate that their T cell receptor (TCR) repertoire is highly diverse and is distinct for iNKT cells resident in individual tissues resulting in differential lipid-antigen recognition. Within peripheral tissues, the TCR repertoire of iNKT cell recent thymic emigrants is different from that of mature cells, indicating that the iNKT population is shaped after their arrival to the tissues. Accordingly, in homeostatic conditions the repertoire of iNKT cells is modulated by tissue-specific signals that control iNKT cell activation and proliferation resulting in differential clonal expansion found for cells resident in various organs. Moreover, the iNKT cell TCR repertoire changes in response to lipid immunization and is shaped by age and by environmental changes. Thus, post-thymic modification of the iNKT cell TCR repertoire underpins the distinct antigen specificity of iNKT cells residing in peripheral tissues iNKT cells were sort-purified from lymphoid tissues from 6-week old WT C57BL/6 mice (as CD1d-tetramer+TCR-b+B220-CD11b-CD11c-). Four biological replicates were performed. Tissues: spleen, thymus, mesenteric lymph node (mLN), inguinal lymph node (iLN)