Eric Espinosa ^1,2* Louise Battut ^1,2 Edouard Leveque ^2,3 Salvatore Valitutti ^2,3 Nicolas Cenac ^1,2 Gilles DIETRICH ^1,2

• ¹ INSERM U1220 Institut de Recherche en Santé Digestive, Toulouse, France
• ² Université Toulouse III Paul Sabatier, Toulouse, Occitanie, France
• ³ INSERM U1037 Centre de Recherche en Cancérologie de Toulouse, Toulouse, Midi-Pyrénées, France

is an alarmin released by epithelial cells in response to tissue damage. It activates resident immune sentinel cells, which then produce signals commonly associated with type 2 immune responses, particularly affecting infiltrating antigen-specific T cells. Given that mast cells (MCs) are a primary target of IL-33 and can shape T helper (Th) cell responses, we investigated the effect of IL-33 priming on the ability of MCs to influence Th cell cytokine production. To examine the Th cell/MC interaction, we developed human primary MC/memory CD4 + T cell coculture systems involving both cognate and non-cognate interactions. Our results demonstrated that IL-33-primed MCs, whether as bystander cells cocultured with activated effector T cells or functioning as antigenpresenting cells, promoted IL-9 and increased IL-13 production in Th cells via an OX40L-dependent mechanism. This indicates that MCs sense IL-33-associated danger, prompting them to direct Th cells to produce the key type 2 effector cytokines IL-9 and IL-13.with Th cells and influence their polarization. We showed that IL-33-primed MCs fostered Th2 cell responses and let emerge IL-9 producing Th cells in an OX40L-dependent manner.provide cues required by infiltrated Th cells to produce their cytokines and also signals that mold the panel of produced cytokine, here IL-9 and IL-13 via OX40-OX40L interaction.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.