How the immune system signals to hematopoietic stem cells?

by on August 4, 2008 · 0 comments

in Journal club

Blogging on Peer-Reviewed ResearchHow the immune system signals to hematopoietic stem cells (HSCs) is a very interesting and hot topic. To understand the dynamics of this communication, both during steady-state and under specific challenge, it is necessary to understand how the myriad incoming signals are processed so the outcome is a meaningful response. Each stimulus and its response is another little piece that helps us understand this system. This understanding, in turn, is key to successfully and specifically manipulating the system’s components, which has great therapeutic potential.

Lrg47 (Irgm1) is an interferon-induced GTPase, which functions to transduce some signals by hydrolyzing GTP bound to specific proteins. It has previously only been described in context of immune function, but a recent finding now links it to hematopoiesis.

Irgm1 is critical to the immune response to intacellular bacteria. In macrophages, Irgm1 is a negative regulator of proinflammatory cytokine signaling following stimulation of TLR4 (M.avium is recognized through this receptor). Animals deficient in Irgm1 die from shock after bacterial LPS injection.

Now, new findings suggest that Irgm1 has been linked to HSC proliferation. Carl Feng and colleagues from describes the role of Irgm1 in mediating immune communication to HSCs during specific immunologic challenge. The authors detail (through in vivo studies on knockout mice) how Irgm1 affects HSCs. A summary of the findings:


• Irgm-1 is induced in HSCs one day after “stress-treatment” and after M. avium challenge
• In Irgm1 -/- mice:
* HSCs showed impaired reconstitution after ablation
* HSCs showed poorer engraftment than those in normal (wild type) mice
* LT HSCs had a higher rate of proliferation at steady-state than those in wild type
* HSCs expanded later and to a lesser degree after challenge with M.avium than those in normal mice.

So, taken together, Irgm1 shows a capacity to negatively regulate HSC proliferation until it is specifically induced to do exactly the opposite.

So what does Irgm1 signaling tell us about how the immune system and HSCs communicate? And what does it tell us about inter-system communication in general? The paper by Feng et al shows an interferon-responsive gene active in non-immune cells (HSCs). It’s especially interesting because the same gene is also active in immune cells, exerting anti-inflammatory effects. How Irgm1 also causes HSC expansion adds complexity to its signaling network but reduces the overall number of signaling molecules involved. It will be interesting to know at a molecular biology level what Irgm1 does (what exactly does it interact with?) because that will likely uncover some new connections that will further illuminate the immune response.

Cell Stem Cell 2008;2:83-89
discussion about this study

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