Ingred Wilson

Publications (2)6.96 Total impact

• Article: Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling.

  Jianmin Su, Qifa Xie, Ingred Wilson, Liwu Li
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  ABSTRACT: Toll-like-receptor mediated signaling is finely regulated by a complex intracellular protein network including the interleukin-1 receptor associate kinases (IRAKs). IRAK-4, 1, and 2 may positively regulate innate immunity signaling through the activation of various downstream kinases such as MAPKs. In contrast, IRAK-M plays an inhibitory role through unknown mechanism. In this report, we show that IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. Furthermore, using bone marrow derived macrophages (BMDM) from wild type, IRAK1(-/-), and IRAK-M(-/-) mice, we have herein demonstrated that IRAK-M selectively attenuates bacterial lipopeptide Pam(3)CSK(4)-induced p38 activation, but not ERK or JNK. IRAK1(-/-) and IRAK-M(-/-)BMDM display distinct activation profile of various MAP kinases upon Pam(3)CSK(4) challenge, indicating that IRAK-M exerts its inhibitory effect through an IRAK1 independent pathway. Pam(3)CSK(4) challenge leads to rapid decrease of MKP-1 protein level in IRAK-M(-/-)BMDM as well as THP-1 cells with decreased IRAK-M expression through siRNA interference. Our findings indicate that IRAK-M selectively attenuates p38 activation and inhibits innate immunity through stabilizing MKP-1.
  Cellular Signalling 08/2007; 19(7):1596-601. · 4.06 Impact Factor
• Article: Loss of the innate immunity negative regulator IRAK-M leads to enhanced host immune defense against tumor growth.

  Qifa Xie, Lu Gan, Jianxia Wang, Ingred Wilson, Liwu Li
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  ABSTRACT: IRAK-M is a negative regulator of innate immunity signaling processes. Although attenuation of innate immunity may help to prevent excessive inflammation, it may also lead to compromised immune surveillance of tumor cells and contribute to tumor formation and growth. Here, we demonstrate that IRAK-M(-/-) mice are resistant to tumor growth upon inoculation with transplantable tumor cells. Immune cells from IRAK-M(-/-) mice are responsible for the anti-tumor effect, since adoptive transfer of splenocytes from IRAK-M(-/-) mice to wild type mice can transfer the tumor-resistant phenotype. Upon tumor cell challenge, there are elevated populations of CD4(+) and CD8(+) T cells and a decreased population of CD4(+) CD25(+)Foxp3(+) regulatory T cells in IRAK-M(-/-) splenocytes. Furthermore, we observe that IRAK-M deficiency leads to elevated proliferation and activation of T cells and B cells. Enhanced NFkappaB activation directly caused by IRAK-M deficiency may explain elevated activation of T and B cells. In addition, macrophages from IRAK-M(-/-) mice exhibit enhanced phagocytic function toward acetylated LDL and apoptotic thymocytes. Collectively, we demonstrate that IRAK-M is directly involved in the regulation of both innate and adaptive immune signaling processes, and deletion of IRAK-M enhances host anti-tumor immune response.
  Molecular Immunology 08/2007; 44(14):3453-61. · 2.90 Impact Factor