ILC2s in High Definition: Decoding the Logic of Tissue-Based Immunity

Group 2 innate lymphoid cells (ILC2s) mediate allergic immunity but have also recently come into focus as key sentinels of tissue health and homeostasis. Clues as to how these rare immune cells coordinate tissue-wide responses to perturbation have emerged from deciphering the communication between ILC2s and an ever-expanding list of diverse nonhematopoietic cells. High-resolution tracking and profiling approaches have accelerated these efforts, revealing ILC2 transcriptional programs that are coordinated with tissue and organism development. We propose that the engagement of these homeostatic feedback circuits by internal and external cues forms the basis for how tissues instruct type 2 immunity. Understanding how these normally restorative networks become unbalanced may be crucial in devising appropriately targeted therapies for allergic diseases.