H2-Eb1, the mouse ortholog of human HLA-DRB1, is associated with the major histocompatibility complex class II (MHC-II) and plays a role in antigen presentation, which is crucial for the adaptive immune response. It is involved in pathways related to immune cell activation and the regulation of the Th1/Th2 balance [1,2,3,4,6,9]. Genetic models, such as knockout mice, are valuable tools for studying its function.

In allergic rhinitis (AR) mouse models, knockout of H2-Eb1 alleviated AR symptoms. H2-Eb1 knockout mice had increased serum OVA-IgE and IL-4 levels, decreased IFN-γ levels compared to the control group. Homozygous (-/-) knockout mice had milder allergic symptoms than heterozygous (+/-) ones, indicating H2-Eb1 may play a role in regulating Th1/Th2 balance during AR pathogenesis [1]. Mice with double knockout of H2-Eb1 and H2-Ab1 also showed reduced susceptibility to AR, with fewer histological changes in nasal mucosal tissue, reduced eosinophilic granulocytes, mast cells, OVA-specific IgE, and IL-13 levels, and increased IL-2 levels [3].

In the context of Parkinson's disease in the Line 61-PFF mouse model, inhibiting the JAK/STAT pathway reduced the expression of H2-Eb1 in the MM4 cluster, which was associated with a decrease in neuroinflammatory responses [4,6].

In the aging kidney, the expression of H2-Eb1 was associated with a "tubuloinflammaging" phenotype [5].

In the testis of db/db mice, the expression of H2-Eb1 was elevated, along with other genes, suggesting its involvement in steroidogenesis and spermatogenesis impairment [7].

In a mouse heart transplant model, HHT treatment downregulated the expression of H2-Eb1 and promoted heart allograft acceptance by enhancing regulatory T cells induction [8].

During aging in mice, classical monocytes from the bone marrow had higher expression of H2-Eb1 and more of them expressed MHCII, suggesting its role in age-associated changes in monocyte function [9].

In conclusion, H2-Eb1 is essential for antigen presentation and immune response regulation. Gene knockout mouse models have revealed its significance in various disease areas such as allergic rhinitis, Parkinson's disease, aging-related kidney phenotypes, testicular function, heart allograft acceptance, and age-associated monocyte function changes. These findings help in understanding the biological functions of H2-Eb1 and provide insights into the mechanisms of related diseases.

References:

1. Li, Linge, Hu, Bin, Feng, Juan, Jiang, Chunrong, Zhang, Hua. . H2-EB1 Molecule Alleviates Allergic Rhinitis Symptoms of H2-Eb1 Knockout Mice. In Iranian journal of immunology : IJI, 12, 263-73. doi:. https://pubmed.ncbi.nlm.nih.gov/26714418/

2. Zhang, Yu, Feng, Juan, Sun, Jie, Liu, Hui, Zhang, Hua. . H2-Eb1 expression is upregulated in the nasal mucosa of allergic rhinitis. In Asian Pacific journal of allergy and immunology, 32, 308-15. doi:10.12932/AP0478.32.4.2014. https://pubmed.ncbi.nlm.nih.gov/25543041/

3. Tang, Zhiyuan, Wang, Yan, Lv, Liang, Li, Linge, Zhang, Hua. 2018. Mice with double knockout of H2-Eb1 and H2-Ab1 exhibit reduced susceptibility to allergic rhinitis. In PloS one, 13, e0206122. doi:10.1371/journal.pone.0206122. https://pubmed.ncbi.nlm.nih.gov/30372475/

4. Hong, Huixian, Wang, Yong, Menard, Marissa, Qin, Hongwei, Benveniste, Etty N. 2024. Suppression of the JAK/STAT pathway inhibits neuroinflammation in the line 61-PFF mouse model of Parkinson's disease. In Journal of neuroinflammation, 21, 216. doi:10.1186/s12974-024-03210-8. https://pubmed.ncbi.nlm.nih.gov/39218899/

5. Sinning, Julius, Funk, Nils David, Soerensen-Zender, Inga, Melk, Anette, Schmitt, Roland. 2023. The aging kidney is characterized by tubuloinflammaging, a phenotype associated with MHC-II gene expression. In Frontiers in immunology, 14, 1222339. doi:10.3389/fimmu.2023.1222339. https://pubmed.ncbi.nlm.nih.gov/37675124/

6. Hong, Huixian, Wang, Yong, Menard, Marissa, Qin, Hongwei, Benveniste, Etty. 2024. Suppression of the JAK/STAT Pathway Inhibits Neuroinflammation in the Line 61-PFF Mouse Model of Parkinson's Disease. In Research square, , . doi:10.21203/rs.3.rs-4307273/v1. https://pubmed.ncbi.nlm.nih.gov/38766241/

7. Hu, Yun, Cai, Ting-Ting, Yan, Reng-Na, Ding, Bo, Ma, Jian-Hua. 2024. Single-Cell RNA Sequencing Analysis of Steroidogenesis and Spermatogenesis Impairment in the Testis of db/db Mice. In International journal of endocrinology, 2024, 8797972. doi:10.1155/2024/8797972. https://pubmed.ncbi.nlm.nih.gov/38817616/

8. Qiu, Xia, Zhang, Hedong, Tang, Zhouqi, Peng, Longkai, Dai, Helong. 2023. Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model. In Chinese medical journal, 137, 1453-1464. doi:10.1097/CM9.0000000000002813. https://pubmed.ncbi.nlm.nih.gov/37962205/

9. Barman, Pijus K, Shin, Juliana E, Lewis, Sloan A, Benayoun, Bérénice A, Goodridge, Helen S. 2022. Production of MHCII-expressing classical monocytes increases during aging in mice and humans. In Aging cell, 21, e13701. doi:10.1111/acel.13701. https://pubmed.ncbi.nlm.nih.gov/36040389/