Postdoctoral Researcher Brown Univ. Providence, Rhode Island, United States
Disclosure(s):
Jacob Myers, PhD: No financial relationships to disclose
Introduction/Rationale: Group 1 ILCs, composed of conventional NK cells (cNK), tissue resident NK cells (trNK) and ILC1s, are critical mediators of anti-viral immunity in lymphoid and non-lymphoid tissues. Within this group, it is understood that cNK act as the circulating, cytotoxic population, while trNK and ILC1s provide regulatory protection within tissues. Krüppel-like factor 2 (KLF2) is a transcription factor that controls the migration and activation of various lymphocytes. Recent work has demonstrated that KLF2 is a distinguishing factor for group 1 ILCs with cNK cells expressing KLF2 and trNK and ILC1s largely lacking KLF2 expression. However, its role in shaping the function, development, and residency patterns of group 1 ILCs remain poorly understood.
Methods: To address this gap in knowledge, we generated conditional knockout (cKO) mice in the group 1 ILC lineage (NCR1-Cre KLF2 fl/fl) and evaluated cell distribution across tissues.
Results: In lymphoid tissues (i.e. blood, spleen, bone marrow) KLF2 deficiency resulted in a reduction in mature NK cells and a significant increase in immature NK cell subsets. The abundance of trNK and ILC1 in non-lymphoid tissues (i.e. uterus, pancreas, salivary gland) was not affected. Despite their lack of circulating mature NK cells, cKO animals showed no differences in morbidity relative to control animals following MCMV infection. However, Ncr1-Cre-Rosa-DTA mice, which lack all group 1 ILCs, exhibited significantly greater weight loss, suggesting that mature, circulating conventional NK cells are dispensable for preventing excess morbidity during acute infection.
Conclusion: These data highlight an unappreciated role for KLF2 in controlling Group 1 ILC1 maturation, residency, and function across lymphoid and non-lymphoid tissues. Despite their well known ability to control MCMV infection, our data demonstrate that tissue resident group 1 ILCs are sufficient for preventing excess morbidity during acute infection.
