Increased NKp44 (−) ILC3s in the peripheral blood of patients with Crohn’s disease

Abstract

Abstract Crohn’s disease (CD) is a complex chronic immune-mediated disorder of the human gastrointestinal tract. Emerging evidence indicates an essential role of the innate immunity in this process. Newly identified innate lymphoid cells (ILCs) are important components of the innate immunity. They act as the first line of defense to eliminate the invading pathogens. Previously, we have reported that IFN-γ-producing CD127 (+) ILC1 subset accumulated in the inflamed terminal ileum of CD patients at the expense of IL-22-producing NKp44 (+) ILC3s. This ILC phenotypic alteration was associated with the expansion of pathogenic Th17/Th1 subset among the diseased tissues. In order to further understand the contribution of ILCs to the pathogenesis of CD, we evaluated the aberrant ILCs’ responses in the peripheral blood of active CD patients in this study. We noticed that the frequency of IFN-γ-producing-CD127 (+) ILC1s was increased in the circulation of CD patients compared to donors. Furthermore, the frequency of NKp44 (−) CD117 (+) ILC3s was also significantly increased. Interestingly, they did not produce any of the common ILC cytokines: IL-17A, IL-22 and IFN-γ which is consistent with their ILC progenitor status in recent reports. In addition, almost half of the NKp44 (−) CD117 (+) ILC3s in the peripheral blood of CD patients were HLA-DR (MHC-II) positive which reveals their potential to interact and regulate systemic adaptive immunity, especially CD4 T cell responses. Different from ILC1s and ILC3s, the frequency of CRTH2 (+) ILC2s was decreased. More detailed analysis of the dysregulated innate and adaptive immune responses will help us to better understand the mechanism of CD pathogenesis and develop more novel therapeutic strategies.