Rab44 Deficiency Induces Impaired Immune Responses to Nickel Allergy

• Published in: International journal of molecular sciences 2023-01, Vol.24 (2), p.994
• Main Authors: Noguromi, Mayuko, Yamaguchi, Yu, Sato, Keiko, Oyakawa, Shun, Okamoto, Kuniaki, Murata, Hiroshi, Tsukuba, Takayuki, Kadowaki, Tomoko
• Format: Article
• Language: English
• Subjects: Allergies; Animals; Biocompatibility; Blood; Bone marrow; C-Terminus; Cell differentiation; Cell number; Cytokines; Dermatitis; Differentiation (biology); differentiation of blood cells; Domains; EF-hand; Granulocytes; Hematology; Histamine; Hypersensitivity; Hypersensitivity - genetics; Immune response; immune responses; Immune system; Immunity; Immunology; Inflammation; Interleukin 10; Leukocytes (granulocytic); Lipopolysaccharides; Lipopolysaccharides - toxicity; Lymphocytes; Macrophages; Mast cells; Mice; Mutation; N-Terminus; Nickel - toxicity; nickel allergy; Osteoclasts; Proteins; rab GTP-Binding Proteins - genetics; rab GTP-Binding Proteins - metabolism; Rab44; Stimulation; Toxicity; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24020994

Rab44 was recently identified as an atypical Rab GTPase that possesses EF-hand and coiled-coil domains at the N-terminus, and a Rab-GTPase domain at the C-terminus. Rab44 is highly expressed in immune-related cells such as mast cells, macrophages, osteoclasts, and granulocyte-lineage cells in the bone marrow. Therefore, it is speculated that Rab44 is involved in the inflammation and differentiation of immune cells. However, little is known about the role of Rab44 in inflammation. In this study, we showed that Rab44 was upregulated during the early phase of differentiation of M1- and M2-type macrophages. Rab44-deficient mice exhibited impaired tumor necrosis factor alpha and interleukin-10 production after lipopolysaccharide (LPS) stimulation. The number of granulocytes in Rab44-deficient mice was lower, but the lymphocyte count in Rab44-deficient mice was significantly higher than that in wild-type mice after LPS stimulation. Moreover, Rab44-deficient macrophages showed impaired nickel-induced toxicity, and Rab44-deficient mice showed impaired nickel-induced hypersensitivity. Upon nickel hypersensitivity induction, Rab44-deficient mice showed different frequencies of immune cells in the blood and ears. Thus, it is likely that Rab44 is implicated in immune cell differentiation and inflammation, and Rab44 deficiency induces impaired immune responses to nickel allergies.