The signature hallmark of adaptive immunity is the evolution of somatically rearranged antigen receptors, which confer both diversity and specificity to T and B lymphocytes. For decades, immunologists have observed cells which possess lymphoid characteristics yet lack such antigen-specific receptors. Collectively, these populations are referred to as innate lymphoid cells (ILCs) (Vivier et al. in Cell 174(5):1054–1066, 2018). Cytotoxic natural killer (NK) cells and lymphoid tissue-inducing cells (LTi), which contribute to the formation of lymphoid organs during embryogenesis, are the earliest described ILCs. Subsequently, diverse populations of ILCs have been described based on the signature cytokines they produce. Group 1 ILCs (ILC1) produce IFNγ, group 2 ILCs (ILC2) produce IL-5 and IL-13, and group 3 ILCs (ILC3) produce IL-22 and IL-17. In contrast to adaptive lymphocytes which take several days to undergo clonal expansion and acquire effector functions, ILCs secrete cytokines rapidly in response to activating signals in their tissue of residence. ILCs may also directly regulate adaptive lymphocytes and myeloid cells through co-stimulatory molecules and soluble factors. Thus, ILCs play important roles in both the initiation and amplification of the immune response. When properly regulated, ILCs maintain intestinal homeostasis and protect the host from infection by various pathogens. However, dysregulation of mucosal immunity drives intestinal inflammation and contributes to pathology, such as inflammatory bowel disease (IBD). In this review, we outline the roles that ILCs play in amplifying or regulating intestinal inflammation as well as ongoing efforts to target these disease mechanisms for IBD therapy.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
Number of pages16
StatePublished - 2022

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • IBD
  • ILC
  • Inflammatory bowel disease
  • Innate lymphoid cells
  • Mucosal immunity


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