|Title||Neuropeptide CGRP Limits Group 2 Innate Lymphoid Cell Responses and Constrains Type 2 Inflammation.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Nagashima H, Mahlakõiv T, Shih H-Y, Davis FP, Meylan F, Huang Y, Harrison OJ, Yao C, Mikami Y, Urban JF, Caron KM, Belkaid Y, Kanno Y, Artis D, O'Shea JJ|
|Date Published||2019 Jul 16|
Innate lymphocytes maintain tissue homeostasis at mucosal barriers, with group 2 innate lymphoid cells (ILC2s) producing type 2 cytokines and controlling helminth infection. While the molecular understanding of ILC2 responses has advanced, the complexity of microenvironmental factors impacting ILC2s is becoming increasingly apparent. Herein, we used single-cell analysis to explore the diversity of gene expression among lung lymphocytes during helminth infection. Following infection, we identified a subset of ILC2s that preferentially expressed Il5-encoding interleukin (IL)-5, together with Calca-encoding calcitonin gene-related peptide (CGRP) and its cognate receptor components. CGRP in concert with IL-33 and neuromedin U (NMU) supported IL-5 but constrained IL-13 expression and ILC2 proliferation. Without CGRP signaling, ILC2 responses and worm expulsion were enhanced. Collectively, these data point to CGRP as a context-dependent negative regulatory factor that shapes innate lymphocyte responses to alarmins and neuropeptides during type 2 innate immune responses.
|Grant List||U01 AI095608 / AI / NIAID NIH HHS / United States|