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Reviewer #2: An understanding of early signaling pathways that mediate tissue injury is critical for the development of effective therapeutic strategies in the treatment of various immunological diseases. In the review, the authors provide an overview about the function of XXX and discusstheir potential role in immune regulation and autoimmunity. While the manuscript is of great interest, there are several concerns need to beaddressed.

Concerns:
1. Strong English language editing is necessary.
2. Complete reference citation is required; see for example Wang et al., Perry et al.
3. Figures 1 and 2 are redundant and without relevance to the topics discussed in the review and should therefore be omitted. Instead, a Figure which summarizes the involvement of distinct XXX at different levels of autoimmunity is strongly recommended.
4. There is a dispute in the field about the genetic background versus housing conditions for spanteneous XXX in XXX-deficientmice. This needs to be discussed with references of recent publications.
5. Table 1: The statement of defective macrophage phagocytosis in XXX deficiency is wrong (see Wang et al.). Also, defective neutrophil recruitment should be more specified, since XXX null PMN migrate normally to chemotactic gradients but are defective to cross epithelial /endothelial barriers

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