MILR1, also known as mast cell immunoglobulin-like receptor 1 or Allergin-1, is an inhibitory immunoreceptor. It plays a crucial role in the immune system, especially in suppressing immunoglobulin E (IgE)-mediated, mast cell-dependent responses [1]. It is associated with pathways related to immune regulation and may influence the communication between cells like mast cells and microglia, which is important for central nervous system (CNS) homeostasis [2].

In Milr1-deficient (Milr1-/-) mice, more severe hypothermia, higher mortality rate, and greater incidence of diarrhea were observed in an oral ovalbumin-induced food allergy model compared to wild-type mice. Depletion of basophils rescued Milr1-/-mice from lethal hypothermia but not from diarrhea, suggesting that Allergin-1 on basophils selectively suppresses oral allergen-induced anaphylaxis [3]. Also, Milr1-/-mice exhibited more severe dextran sulfate sodium (DSS)-induced colitis and enhanced intestinal permeability. Treatment with neomycin restored intestinal barrier integrity, and 16S rRNA gene sequencing analysis showed changes in gut microbiota, indicating that Allergin-1 deficiency leads to intestinal dysbiosis and barrier dysfunction [4].

In conclusion, MILR1 is an important inhibitory immunoreceptor that plays a significant role in immune-related processes. The study of Milr1-/-mouse models has revealed its functions in suppressing anaphylaxis and maintaining intestinal homeostasis, providing insights into its potential role in allergic and gastrointestinal diseases.

References:

1. Nanatsue, Kentaro, Ninomiya, Takahiro, Tsuchiya, Mio, Arinami, Tadao, Noguchi, Emiko. 2014. Influence of MILR1 promoter polymorphism on expression levels and the phenotype of atopy. In Journal of human genetics, 59, 480-3. doi:10.1038/jhg.2014.57. https://pubmed.ncbi.nlm.nih.gov/25007884/

2. Khayer, Nasibeh, Motamed, Nasrin, Marashi, Sayed-Amir, Goshadrou, Fatemeh. 2023. RT-DOb, a switch gene for the gene pair {Csf1r, Milr1}, can influence the onset of Alzheimer's disease by regulating communication between mast cell and microglia. In PloS one, 18, e0288134. doi:10.1371/journal.pone.0288134. https://pubmed.ncbi.nlm.nih.gov/37410787/

3. Lin, Yu-Hsien, Tahara-Hanaoka, Satoko, Nagai, Kei, Karasuyama, Hajime, Shibuya, Akira. . Selective suppression of oral allergen-induced anaphylaxis by Allergin-1 on basophils in mice. In International immunology, 32, 213-219. doi:10.1093/intimm/dxz075. https://pubmed.ncbi.nlm.nih.gov/31793637/

4. Lin, Yu-Hsien, Tahara-Hanaoka, Satoko, Obana, Nozomu, Fukuda, Shinji, Shibuya, Akira. . An inhibitory immunoreceptor Allergin-1 regulates the intestinal dysbiosis and barrier function in mice. In International immunology, 36, 365-371. doi:10.1093/intimm/dxae010. https://pubmed.ncbi.nlm.nih.gov/38442194/