Authors: Xiaotian Ju, Nahal Emami Fard, Anurag Bhalla, Anna Dvorkin-Gheva, Maria Xiao, Katherine Radford, Kayla Zhang, Reina Ditta, John Paul Oliveria, Guillaume Paré, Manali Mukherjee, Parameswaran Nair, Roma Sehmi
Published: 2025-01-15
DOI: 10.1126/scitranslmed.ado6649
Source: Full article
In prednisone-dependent severe asthma, uncontrolled sputum eosinophilia is associated with increased numbers of group 2 innate lymphoid cells (ILC2s). These cells represent a relatively steroid-insensitive source of interleukin-5 (IL-5) and IL-13 and are considered critical drivers of asthma pathology. The abundance of ILC subgroups in severe asthma with neutrophilic or mixed granulocytic (both eosinophilic and neutrophilic) airway inflammation, prone to recurrent infective exacerbations, remains unclear. Here, we found by flow cytometry that sputum ILC3s are increased in severe asthma with intense airway neutrophilia, whereas equivalently raised sputum ILC2s and ILC3s were found in severe asthma with mixed granulocytic inflammation. Unbiased clustering analyses identified an “intermediate-ILC2” population displaying markers of both ILC2s (prostaglandin D