May 5, 2026 | By Asher Jones
New research published in Nature Immunology shows that a transcription factor called BLIMP1 is essential for maintaining the identity of type 2 innate lymphoid cells (ILC2s) in a mouse model of allergic asthma, shedding light on how these cells promote allergy in asthmatic patients.
The immune system can invoke one of several major programs when it encounters a threat: Type 1 immunity neutralizes intracellular pathogens such as viruses and bacteria, and type 2 helps expel parasitic worms and neutralize toxins. While overactive type 1 immunity can lead to autoimmunity, dysregulation of type 2 leads to inflammatory conditions such as allergic asthma and food allergies.
ILCs are a type of innate immune cell that live within tissues such as the lung, where they respond to general danger signals such as tissue damage, rather than responding to specific antigens like T cells and other adaptive immune cells do.
“Similar to T cells, ILCs have inherent plasticity,” said senior author Amanda Poholek, associate professor of immunology at the University of Pittsburgh School of Medicine. “In the lung, ILC2 cells, which normally secrete type 2 cytokines in response to stimulation, can shift to express type 1 cytokines in response to infection like influenza. The regulators that allow for this plasticity or limit this plasticity had not been well described.”
In a 2024 Nature Immunology study, Poholek and her team previously showed that BLIMP1 is required for the formation of T helper 2 (Th2) cells in a mouse model of allergic asthma, so she hypothesized that BLIMP1 may also play a role in ILC2 identity, too.
BLIMP1 is also a regulator of B cells. See: BLIMP1 Acts as a Molecular Brake to Balance B Cell Breadth
To answer this question, the researchers started by showing that BLIMP1 is upregulated in ILC2s in mice in response to common allergens: house dust mite, a protein called papain, and fungal spores. These allergens switch on tissue alarmins, or signaling proteins, called IL-33 and IL-25, which induce IL-9, which in turn upregulate BLIMP1.
Then they compared normal mice to those that lacked BLIMP1 specifically in their ILC2s. In absence of BLIMP1, they saw an increase in type 1 cytokines and a decrease in most type 2 cytokines, leading to an overall decrease in allergic asthma symptoms.
Mice that lacked BLIMP1 had less inflammation, less mucus production in the lungs, and fewer eosinophils, a white blood cell associated with asthma.
When BLIMP1 is switched off in ILC2 cells, mouse lungs show far less inflammation and mucus buildup after allergen exposure (right) compared to lungs of control mice (left). CREDIT: Zheng et al., 2026; Nature Immunology
“When we deleted BLIMP1, we saw a loss of type 2 identity in ILC2s,” said Poholek. “BLIMP1 limits ILC2 plasticity and maintains type 2 status to drive allergic asthma symptoms.”
Surprisingly, though, they also saw an increase in IL-9 and mast cells—another type of allergy-related cell—in the animals lacking BLIMP1.
According to Poholek, this mixed inflammatory state of high mast cells and low eosinophils in mice resembles some features of a subset of patients with severe mixed inflammatory type asthma.
“We think that this BLIMP1 mouse model could allow us to better tease out the relative roles of mast cell-driven and eosinophil-driven inflammation in severe asthma and more precisely target these mechanisms,” she said.
Poholek is also interested in understanding what happens in the lung during respiratory viral exacerbation of asthma, which involves both type 1 and type 2 responses. She also plans to investigate the role of ILCs in lung cancer and whether modulating their identity by targeting BLIMP1 or other upstream drivers could promote anti-tumor immunity.