2020年11月5日 · Here we report on the discovery of a germline GOF JAK3 mutation as a first germline cause of CLPD-NK. Two individuals from one nonconsanguineous family (mother and son) presented at ages 35 and 12 years old with NK cell lymphoproliferation, lymphadenopathy, splenomegaly and autoimmune symptoms.

2019年11月1日 · JAK3 is a JAK family member that is involved in NK cell development, proliferation, and function (Ghoreschi et al., 2009). In contrast with other JAK members, JAK3 expression is restricted to hematopoietic tissues ( Thomis and Berg, 1997 ).

2019年11月11日 · Jak3 −/− mice are immunocompromised, display severe developmental defects in the lymphoid lineage and lack NK, T and B cells (23, 53). The in vivo administration of Tofacitinib, which predominantly inhibits JAK3 and to a lesser degree JAK1 and JAK2, depletes all NK cell subsets in the periphery of rhesus macaques ( 54 ).

2019年11月12日 · Natural Killer (NK) cells are cytotoxic lymphocytes of the innate immune system and play a critical role in anti-viral and anti-tumor responses. NK cells develop in the bone marrow from hematopoietic stem cells (HSCs) that differentiate through common lymphoid progenitors (CLPs) to NK lineage-restri …

Germline JAK3 GOF mutations have also been identified in the context of familial chronic lymphoproliferative disorder of NK cells (CLPD-NKs) . JAK3 has further been observed to be constitutively activated in a range of lymphoid malignancies even when not mutated, such as a cohort of peripheral T cell lymphoma (PTCL) patients positive for ALK ...

Janus kinase (JAK)-signal transducer and activators of transcription (STAT) signaling pathways play crucial roles in lymphopoiesis. In particular, JAK3 has unique functions in the lymphoid system such that JAK3 ablation results in phenotypes ...

2019年9月19日 · The identification of recurrent mutations in NK-cell enteropathy support a neoplastic origin, and it may be considered a distinct neoplastic disease entity with the following diagnostic criteria: indolent clinical behavior but chronic, recurring course; dense superficial mucosal lymphoid infiltrate by lymphoid cells with mild cytological atypia ...

2024年3月4日 · The structure, function and impacts of both GOF and LOF mutations of JAK3 are highly conserved, making animal models highly informative. This review details the biology of JAK3 and the impact of its perturbation in immune cell …

2019年12月18日 · We assessed the effects of in vivo administration of a JAK1/3 inhibitor, tofacitinib, vs. a more selective JAK3 inhibitor, PF-06651600, focusing on NK cells from spleen, liver and BM and ILC1 from liver. Our data revealed differential effects of these JAKinibs on the NK cell and ILC1 numbers, the latter subset being less sensitive to JAK ...

Extranodal, nasal-type natural killer (NK)/T-cell lymphoma (NKCL) is an aggressive malignancy with poor prognosis in which, usually, signal transducer and activator of transcription 3 (STAT3) is constitutively activated and oncogenic. Here, we demonstrate …