Troch Karoline F, Jakob Manuel O, Forster Patrycja M, Jarick Katja J, Schreiber Jonathan, Preusser Alexandra, Guerra Gabriela M, Durek Pawel, Tizian Caroline, Sterczyk Nele, Helfrich Sofia, Duerr Claudia U, Voehringer David, Witkowski Mario, Artis David, Rollenske Tim, Kruglov Andrey A, Mashreghi Mir-Farzin, Klose Christoph S N
Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Microbiology, Infectious Diseases and Immunology, Hindenburgdamm 30, Berlin, Germany.
Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany.
Nat Commun. 2024 Dec 4;15(1):10566. doi: 10.1038/s41467-024-54780-3.
Tissue-resident immune cells, such as innate lymphoid cells, mediate protective or detrimental immune responses at barrier surfaces. Upon activation by stromal or epithelial cell-derived alarmins, group 2 innate lymphoid cells (ILC2s) are a rapid source of type 2 cytokines, such as IL-5. However, due to the overlap in effector functions, it remains unresolved whether ILC2s are an essential component of the type 2 response or whether their function can be compensated by other cells, such as T cells. Here we show a non-redundant role of ILC2s in supporting the development and function of B1 cells. We demonstrate that B1 cells fail to develop properly in the absence of ILC2s and identify the IL-33 receptor on ILC2s as an essential cell-intrinsic regulator of IL-5 production. Further, conditional deletion of Il5 in ILC2s results in defective B1 cell development and immunoglobulin production. Consequently, B1 cells with phosphatidylcholine specific B cell receptor rearrangements are diminished in ILC2-deficient mice. Thus, our data establish an essential function of ILC2s in supporting B1 cells and antibody production at barrier surfaces.
组织驻留免疫细胞，如固有淋巴细胞，在屏障表面介导保护性或有害性免疫反应。在被基质细胞或上皮细胞衍生的警报素激活后，2型固有淋巴细胞（ILC2s）是2型细胞因子（如IL-5）的快速来源。然而，由于效应功能的重叠，ILC2s是否是2型反应的重要组成部分，或者它们的功能是否可以被其他细胞（如T细胞）补偿，仍未得到解决。在这里，我们展示了ILC2s在支持B1细胞发育和功能方面的非冗余作用。我们证明，在没有ILC2s的情况下，B1细胞无法正常发育，并确定ILC2s上的IL-33受体是IL-5产生的关键细胞内在调节因子。此外，在ILC2s中条件性删除Il5会导致B1细胞发育和免疫球蛋白产生缺陷。因此，在缺乏ILC2s的小鼠中，具有磷脂酰胆碱特异性B细胞受体重排的B1细胞减少。因此，我们的数据确立了ILC2s在支持B1细胞和在屏障表面产生抗体方面的重要功能。
