| RRC ID |
88537
|
| Author |
Takami D, Abe S, Shimba A, Asahi T, Cui G, Tani-Ichi S, Hara T, Miyata K, Ikutani M, Takatsu K, Oike Y, Ikuta K.
|
| Title |
Lung group 2 innate lymphoid cells differentially depend on local IL-7 for their distribution, activation, and maintenance in innate and adaptive immunity-mediated airway inflammation.
|
| Journal |
Int Immunol
|
| Abstract |
Interleukin-7 (IL-7) is a cytokine critical for the development and maintenance of group 2 innate lymphoid cells (ILC2s). ILC2s are resident in peripheral tissues such as the intestine and lung. However, whether IL-7 produced in the lung plays a role in the maintenance and function of lung ILC2s during airway inflammation remains unknown. IL-7 was expressed in bronchoalveolar epithelial cells and lymphatic endothelial cells (LECs). To investigate the role of local IL-7 in lung ILC2s, we generated two types of IL-7 conditional knockout (IL-7cKO) mice: Sftpc-Cre (SPC-Cre) IL-7cKO mice specific for bronchial epithelial cells and type 2 alveolar epithelial cells and Lyve1-Cre IL-7cKO mice specific for LECs. In steady state, ILC2s were located near airway epithelia, although lung ILC2s were unchanged in the two lines of IL-7cKO mice. In papain-induced airway inflammation dependent on innate immunity, lung ILC2s localized near bronchia via CCR4 expression, and eosinophil infiltration and type 2 cytokine production were reduced in SPC-Cre IL-7cKO mice. In contrast, in house dust mite (HDM)-induced airway inflammation dependent on adaptive immunity, lung ILC2s localized near lymphatic vessels via their CCR2 expression 2 weeks after the last challenge. Furthermore, lung ILC2s were decreased in Lyve1-Cre IL-7cKO mice in the HDM-induced inflammation because of decreased cell survival and proliferation. Finally, administration of anti-IL-7 antibody attenuated papain-induced inflammation by suppressing the activation of ILC2s. Thus, this study demonstrates that IL-7 produced by bronchoalveolar epithelial cells and LECs differentially controls the activation and maintenance of lung ILC2s, where they are localized in airway inflammation.
|
| Volume |
35(11)
|
| Pages |
513-530
|
| Published |
2023-11-7
|
| DOI |
10.1093/intimm/dxad029
|
| PII |
7231240
|
| PMID |
37493250
|
| MeSH |
Adaptive Immunity
Animals
Cytokines / metabolism
Endothelial Cells / metabolism
Immunity, Innate*
Inflammation
Interleukin-33
Interleukin-7*
Lung
Lymphocytes
Mice
Papain
|
| Resource |
| Mice |
RBRC04944 |
