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Despite recent advances in asthma treatments, the search for novel therapies remains necessary because there are still patients with recurrent asthma exacerbations and poor responses to the existing treatments. Since group 2 innate lymphoid cells (ILC2) play a pivotal role in asthma by triggering and exacerbating type 2 inflammation, controlling ILC2s function is key to combating severe asthma. Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans and are activated both in a T cell receptor-dependent and -independent manner. MAIT cells are composed of MAIT1 and MAIT17 based on the expression of transcription factors T-bet and RORγt, respectively. MAIT cells play pivotal roles in host defense against pathogens and in tissue repair and are essential for the maintenance of immunity and hemostasis. Our recent studies revealed that MAIT cells inhibit both ILC2 proliferation and functions in a mouse model of airway inflammation. MAIT cells may alleviate airway inflammation in two ways, by promoting airway epithelial cell barrier repair and by repressing ILC2s. Therefore, reagents that promote MAIT cell-mediated suppression of ILC2 proliferation and function, or designer MAIT cells (genetically engineered to suppress ILC2s or promote repair of airway damage), may be effective therapeutic agents for severe asthma., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Natural killer (NK) cells play a pivotal role in the immune reaction during the bone marrow allograft rejection. Little is known, however, about the molecular mechanisms underlying the NK cell-mediated allograft recognition and rejection. In this report, we assessed the role of a recently identified NK receptor, killer cell lectinlike receptor 1 (KLRE-1), by generating knock-out mice. KLRE-1-deficient mice were born at an expected frequency and showed no aberrant phenotype on growth and lymphoid development. Nevertheless, KLRE-1-deficient cells showed a severely compromised allogeneic cytotoxic activity compared with the wild-type cells. Furthermore, allogeneic bone marrow transfer culminated in colony formation in the spleen of KLRE-1-deficient mice, whereas no colony formation was observed in wild-type recipient mice. These results demonstrate that KLRE-1 is a receptor mediating recognition and rejection of allogeneic target cells in the host immune system.

Truncation of signal transducer and activator of transcription (STAT) 5 at the carboxy-terminal domain, either by genetic engineering or by proteolytic cleavage, results in generation of dominant-negative forms. A nuclear serine protease expressed in the myeloid precursor cells is known to mediate this cleavage, but other proteases responsible for this reaction were unknown. We found that calpain, a ubiquitously expressed cysteine protease, also trims STAT5 in vivo and in vitro, within the carboxy-terminal domain. Nuclear element is not necessary for calpain-mediated STAT5 cleavage, since this process occurs in platelets. We also found that STAT3 is a substrate for calpain in vivo and in vitro, indicating that calpain-mediated cleavage is a common feature of STAT3 and STAT5. Thus, our study reveals a novel pathway for posttranslational modification of STAT3 and STAT5.