Interleukin 9 mediates T follicular helper cell activation to promote antibody responses

Antigen-specific humoral responses are orchestrated through complex interactions among immune cells in lymphoid tissues, including the collaboration between B cells and T follicular helper (Tfh) cells. Accumulating evidence indicates a crucial role for interleukin-9 (IL-9) in the formation of germin...

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Veröffentlicht in:Frontiers in immunology 2024-09, Vol.15, p.1441407
Hauptverfasser: Sato, Taiki, Ikegami, Ippei, Yanagi, Masahiro, Ohyu, Takeshi, Sugaya, Taiki, Shirato, Shotaro, Tanemoto, Masanobu, Kamiya, Shiori, Kikuchi, Kohei, Kamada, Yuka, Nakata, Takehito, Kamekura, Ryuta, Sato, Akinori, Takano, Ken-Ichi, Miyajima, Masahiro, Watanabe, Atsushi, Ichimiya, Shingo
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Sprache:eng
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Zusammenfassung:Antigen-specific humoral responses are orchestrated through complex interactions among immune cells in lymphoid tissues, including the collaboration between B cells and T follicular helper (Tfh) cells. Accumulating evidence indicates a crucial role for interleukin-9 (IL-9) in the formation of germinal centers (GCs), enhancing the generation of class-switched high-affinity antibodies. However, the exact function of IL-9 in Tfh cell regulation remains unclear. In this study, we examined the humoral immune responses of CD4 Il9ra mice, which lack an IL-9-specific receptor in Tfh cells. Upon intraperitoneal immunization with sheep red blood cells (SRBCs), CD4 Il9ra mice displayed diminished levels of SRBC-specific IgG antibodies in their sera, along with reduced levels of GC B cells and plasma cells. Notably, Il9ra-deficient Tfh cells in the spleen exhibited decreased expression of their signature molecules such as B-cell lymphoma 6, C-X-C chemokine receptor 5, IL-4, and IL-21 compared to control mice. In models of allergic asthma induced by house dust mite (HDM) inhalation, CD4 Il9ra mice failed to elevate serum levels of HDM-specific IgE and IgG. This was accompanied by reductions in Tfh cells, GC B cells, and plasma cells in mediastinal lymph nodes. Furthermore, group 2 innate lymphoid cells (ILC2s) were identified as producers of IL-9 under immunizing conditions, possibly induced by leukotrienes released by activated IgD B cells around the T-B border. These observations may indicate the critical role of IL-9 receptor signaling in the activation of Tfh cells, with ILC2s potentially capable of supplying IL-9 in organized lymphoid tissues.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1441407