The roles of neutrophils in renal inflammation are currently unclear. On examining these cells in the unilateral ureteral obstruction murine model of chronic kidney disease, we found that the injured kidney bore a large and rapidly expanding population of neutrophils that expressed the eosinophil marker Siglec-F. We first verified that these cells were neutrophils. Siglec-F⁺ neutrophils were recently detected in several studies in other disease contexts. We then showed that a) these cells were derived from conventional neutrophils in the renal vasculature by TGF-β1 and GM-CSF; b) they differed from their parent cells by more frequent hypersegmentation, higher expression of profibrotic inflammatory cytokines, and notably, expression of collagen 1; and c) their depletion reduced collagen deposition and disease progression, but adoptive transfer increased renal fibrosis. These findings have thus unveiled a subtype of neutrophils that participate in renal fibrosis and a potentially new therapeutic target in chronic kidney disease.

Purpose:The plasticity of ILC has been reported in vitro and in the microenvironment of the intestine. However, whether ILC plasticity contributes to regulation of the tumor microenvironment remains unknown. In the present study, we explored plasticity of ILCs in human lung cancer. Experimental Design: We analyzed immune subsets and cytokine expression in lung cancers freshly obtained from 80 patients and explored conversion of ILC1 into ILC3 in co-culture with lung cancer cells. Prognostic effects of converted ILC3 and related pathway were evaluated by retrospective cohort composed of 875 lung cancer patients. Results: Low percentages of ILC1, and high percentages of ILC3 were found in pulmonary squamous cell carcinomas (SqCCs) but not adenocarcinomas (ADCs). In non-small cell lung cancers, the percentage of ILC3 was associated with IL-23 expression in tumor cells but not immune cells. In co-cultures, tumor cells of SqCCs converted ILC1 into ILC3 by producing IL-23, thus promoting IL-17-mediated tumor cell proliferation. Consistently, among IL-17⁺ immune cells, the percentages of ILCs were higher in SqCCs than ADCs. Furthermore, the numbers of CD3^-RORgt⁺ ILC3, IL-17 expression level, and IL-23- or IL-17RA-expressing tumor cells were associated with short survival of patients with SqCC but not ADC. Conclusions: Conversion from ILC1 into ILC3 by IL-23-producing SqCCs promotes IL-17-mediated tumor progression, resulting in a poor prognosis.

Ham J, et al. Allergy Asthma Immunol Res. 2022 Jul;14(4):361-378. https://doi.org/10.4168/aair.2022.14.4.361

Innate lymphoid cells (ILCs) are innate lymphocytes that do not express antigen-specific receptors and largely reside and self-renew in mucosal tissues. ILCs can be categorized into three groups (ILC1–3) based on the transcription factors that direct their functions and the cytokines they produce. Their signature transcription factors and cytokines closely mirror those of their Th1, Th2, and Th17 cell counterparts. Accumulating studies show that ILCs are involved in not only the pathogenesis of mucosal tissue diseases, especially respiratory diseases, and colitis, but also the resolution of such diseases. Here, we discuss recent advances regarding our understanding of the biology of ILCs in mucosal tissue health and disease. In addition, we describe the current research on the immune checkpoints by which other cells regulate ILC activities: for example, checkpoint molecules are potential new targets for therapies that aim to control ILCs in mucosal diseases. In addition, we review approved and clinically- trialed drugs and drugs in clinical trials that can target ILCs and therefore have therapeutic potential in ILC-mediated diseases. Finally, since ILCs also play important roles in mucosal tissue homeostasis, we explore the hitherto sparse research on cell therapy with regulatory ILCs. This review highlights various therapeutic approaches that could be used to treat ILC-mediated mucosal diseases and areas of research that could benefit from further investigation.