Lee Yunjin, Ishikawa Tomoe, Lee Hyeseung, Lee Byeongjun, Ryu Changhyeon, Davila Mejia Irene, Kim Minjin, Lu Guangqing, Hong Yujin, Feng Mengyang, Shin Hyeyoon, Meloche Sylvain, Locksley Richard M, Koltsova Ekaterina, Grivennikov Sergei I, Heiman Myriam, Choi Gloria B, Huh Jun R
Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Cell. 2025 Apr 17;188(8):2203-2217.e17. doi: 10.1016/j.cell.2025.03.006. Epub 2025 Apr 7.
Cytokines interact with their receptor complexes to orchestrate diverse processes-from immune responses to behavioral modulation. Interleukin-17A (IL-17A) mediates protective immune responses by binding to IL-17 receptor A (IL-17RA) and IL-17RC subunits. IL-17A also modulates social interaction, yet the role of cytokine receptors in this process and their expression in the brain remains poorly characterized. Here, we mapped the brain-region-specific expression of all major IL-17R subunits and found that in addition to IL-17RA, IL-17RB-but not IL-17RC-plays a role in social behaviors through its expression in the cortex. We further showed that IL-17E, expressed in cortical neurons, enhances social interaction by acting on IL-17RA- and IL-17RB-expressing neurons. These findings highlight an IL-17 circuit within the cortex that modulates social behaviors. Thus, characterizing spatially restricted cytokine receptor expression can be leveraged to elucidate how cytokines function as critical messengers mediating neuroimmune interactions to shape animal behaviors.
细胞因子与其受体复合物相互作用，以协调各种过程——从免疫反应到行为调节。白细胞介素-17A（IL-17A）通过与白细胞介素-17受体A（IL-17RA）和白细胞介素-17受体C（IL-17RC）亚基结合来介导保护性免疫反应。IL-17A还调节社会互动，然而细胞因子受体在这一过程中的作用及其在大脑中的表达仍未得到充分表征。在这里，我们绘制了所有主要IL-17R亚基的脑区特异性表达图谱，发现除了IL-17RA外，IL-17RB（而非IL-17RC）通过其在皮层中的表达在社会行为中发挥作用。我们进一步表明，在皮层神经元中表达的IL-17E通过作用于表达IL-17RA和IL-17RB的神经元来增强社会互动。这些发现突出了皮层内调节社会行为的IL-17回路。因此，表征空间受限的细胞因子受体表达可用于阐明细胞因子如何作为关键信使介导神经免疫相互作用以塑造动物行为。
